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Genome Editing Market: Rise in drug discovery and development activities to drive the market – BioSpace

By daniellenierenberg

Genome Editing Market: Snapshot

Genome editing tools have come a long way from the mid-twentieth century. In 1970s and 1980s, gene targeting was done using largely homologous combination, but was only possible in mice. Since then, the expanding science of genetic analysis and manipulation extended to all types of cells and organisms. Advent of new tools helped scientists achieve targeted DNA double-strand break (DSB) in the chromosome, and is a key pivot on which revenue generation in the genome editing market prospered. New directions for programmable genome editing emerged in the decades of the twenty-first century, expanding the arena.

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Cutting-edge platforms at various points in time continue to enrich genome editing market. Various classes of nucleases emerged, most notable of which is CRISPR-Cas. Research labs around the world have extensively used the platforms in making DSBs at any target of choice. Aside from this, agricultural sciences and medical sectors make substantial use of zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) in genome editing. Strides made in stem cell therapies, particularly in rectifying an aberrant mutation, have boosted the growth of the genome editing market. Genetic diseases such as muscular dystrophy and sickle cell disease present an incredible revenue prospect in the genome editing market. Ongoing research on novel vectors and non-vector approaches are expected to bolster the outlook of the market.

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Genomic editing refers to the strategies and techniques implemented for the modification of target genetic information of any living organism. Genome editing involves gene modification at specific areas through recombinant technology, which increases precision in insertion and decreases cell toxicity. Current advancement in genome editing is based on programmable nucleases. The genome editing market is presently witnessing significant growth due to increase in R&D expenditure, rise in government funding for genomic research, technological advancements, and growth in production of genetically modified crops. Companies have made significant investments in R&D in the past few years to develop cutting-edge technologies, such as, CRISPR and TALEN. For instance, Thermo Fisher Scientific is investing significantly in the development of its CRISPR technology for providing better efficiency and accuracy in research and also to fulfil the unmet demands in research and therapeutics. Cas9 protein and FokI protein have been combined to form a dimeric CRISPR/Cas9 RNA-guided FokI nucleases system, which is expected to have wide range of genome editing applications.

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The genome editing market is growing rapidly due to its application in a large number of areas, such as mutation, therapeutics, and agriculture biotechnology. Genome editing techniques offer large opportunities in crop improvement. However, the real potential of homologous recombination for crop improvement in targeted gene replacement therapy is yet to be realized. Homologous recombination is expected to be used as an effective methodology for crop improvement, which is not possible through transgene addition. Rise in the number of diseases and applications is likely to expand the scope of genome editing in the near future. It includes understanding the role of specific genes and processes of organ specific stem cells, such as, neural stem cells and spermatogonial stem cells. Genome editing has a significant scope to treat genetically affected cells, variety of cancers, and agents of infectious diseases such as viruses, bacteria, parasites, etc. However, genetic alteration of human germline for medicinal purpose has been debated for years. Ethical issues, comprising concern for animal welfare, can arise at all stages of generation and life span of genetically engineered animal.

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The global genome editing market can be segmented based on technology, application, end-user, and geography. In terms of technology, the genome editing market can be categorized into CRISPR, TALEN, ZFN, and other technologies. Bioinformatics has eased the process of data analysis through various technological applications. On the basis of application, the global genome editing market can be classified cell-line engineering, animal genome engineering, plant genome engineering, and others. Based on end-user, the genome editing market can be segmented into pharmaceutical and biotechnological companies and academic and clinical research organizations. In terms of region, the global genome editing market can be segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America is projected to continue its dominance in the global genome editing market owing to high government funding for research on genetic modification in the region. Asia Pacific is a rapidly growing genome editing market due to rise in investments by key players in the region. Rise in drug discovery and development activities, coupled with increasing government initiatives toward funding small and start-up companies in the biotechnology and life sciences industry, is a major factor expected to drive the genome editing market in North America during the forecast period. Players should invest in the emerging economies and the countries of Asia-Pacific like China, South Korea, Australia, India and Singapore in which the genome editing market is expected to grow at rapid pace in future, due to growing funding in research.

Key players operating in the global genome editing market are CRISPR Therapeutics, Thermo Fisher Scientific, GenScript Corporation, Merck KgaA, Sangamo Therapeutics, Inc., Horizon Discovery Group, Integrated DNA Technologies, New England Biolabs, OriGene Technologies, Lonza Group, and Editas Medicine.

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Genome Editing Market: Rise in drug discovery and development activities to drive the market - BioSpace

categoriaSkin Stem Cells commentoComments Off on Genome Editing Market: Rise in drug discovery and development activities to drive the market – BioSpace dataJanuary 18th, 2022
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Stem Cells Applications in Regenerative Medicine and …

By daniellenierenberg

Int J Cell Biol. 2016; 2016: 6940283.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India

Academic Editor: Paul J. Higgins

Received 2016 Mar 13; Accepted 2016 Jun 5.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of specific tissue and/or organ of the patients suffering with severe injuries or chronic disease conditions, in the state where bodies own regenerative responses do not suffice [1]. In the present scenario donated tissues and organs cannot meet the transplantation demands of aged and diseased populations that have driven the thrust for search for the alternatives. Stem cells are endorsed with indefinite cell division potential, can transdifferentiate into other types of cells, and have emerged as frontline regenerative medicine source in recent time, for reparation of tissues and organs anomalies occurring due to congenital defects, disease, and age associated effects [1]. Stem cells pave foundation for all tissue and organ system of the body and mediates diverse role in disease progression, development, and tissue repair processes in host. On the basis of transdifferentiation potential, stem cells are of four types, that is, (1) unipotent, (2) multipotent, (3) pluripotent, and (4) totipotent [2]. Zygote, the only totipotent stem cell in human body, can give rise to whole organism through the process of transdifferentiation, while cells from inner cells mass (ICM) of embryo are pluripotent in their nature and can differentiate into cells representing three germ layers but do not differentiate into cells of extraembryonic tissue [2]. Stemness and transdifferentiation potential of the embryonic, extraembryonic, fetal, or adult stem cells depend on functional status of pluripotency factors like OCT4, cMYC, KLF44, NANOG, SOX2, and so forth [35]. Ectopic expression or functional restoration of endogenous pluripotency factors epigenetically transforms terminally differentiated cells into ESCs-like cells [3], known as induced pluripotent stem cells (iPSCs) [3, 4]. On the basis of regenerative applications, stem cells can be categorized as embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and iPSCs (; ). The transplantation of stem cells can be autologous, allogenic, and syngeneic for induction of tissue regeneration and immunolysis of pathogen or malignant cells. For avoiding the consequences of host-versus-graft rejections, tissue typing of human leucocyte antigens (HLA) for tissue and organ transplant as well as use of immune suppressant is recommended [6]. Stem cells express major histocompatibility complex (MHC) receptor in low and secret chemokine that recruitment of endothelial and immune cells is enabling tissue tolerance at graft site [6]. The current stem cell regenerative medicine approaches are founded onto tissue engineering technologies that combine the principles of cell transplantation, material science, and microengineering for development of organoid; those can be used for physiological restoration of damaged tissue and organs. The tissue engineering technology generates nascent tissue on biodegradable 3D-scaffolds [7, 8]. The ideal scaffolds support cell adhesion and ingrowths, mimic mechanics of target tissue, support angiogenesis and neovascularisation for appropriate tissue perfusion, and, being nonimmunogenic to host, do not require systemic immune suppressant [9]. Stem cells number in tissue transplant impacts upon regenerative outcome [10]; in that case prior ex vivo expansion of transplantable stem cells is required [11]. For successful regenerative outcomes, transplanted stem cells must survive, proliferate, and differentiate in site specific manner and integrate into host circulatory system [12]. This review provides framework of most recent (; Figures ) advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells as the tool of regenerative applications in wildlife conservation.

Promises of stem cells in regenerative medicine: the six classes of stem cells, that is, embryonic stem cells (ESCs), tissue specific progenitor stem cells (TSPSCs), mesenchymal stem cells (MSCs), umbilical cord stem cells (UCSCs), bone marrow stem cells (BMSCs), and induced pluripotent stem cells (iPSCs), have many promises in regenerative medicine and disease therapeutics.

ESCs in regenerative medicine: ESCs, sourced from ICM of gastrula, have tremendous promises in regenerative medicine. These cells can differentiate into more than 200 types of cells representing three germ layers. With defined culture conditions, ESCs can be transformed into hepatocytes, retinal ganglion cells, chondrocytes, pancreatic progenitor cells, cone cells, cardiomyocytes, pacemaker cells, eggs, and sperms which can be used in regeneration of tissue and treatment of disease in tissue specific manner.

TSPSCs in regenerative medicine: tissue specific stem and progenitor cells have potential to differentiate into other cells of the tissue. Characteristically inner ear stem cells can be transformed into auditory hair cells, skin progenitors into vascular smooth muscle cells, mesoangioblasts into tibialis anterior muscles, and dental pulp stem cells into serotonin cells. The 3D-culture of TSPSCs in complex biomaterial gives rise to tissue organoids, such as pancreatic organoid from pancreatic progenitor, intestinal tissue organoids from intestinal progenitor cells, and fallopian tube organoids from fallopian tube epithelial cells. Transplantation of TSPSCs regenerates targets tissue such as regeneration of tibialis muscles from mesoangioblasts, cardiac tissue from AdSCs, and corneal tissue from limbal stem cells. Cell growth and transformation factors secreted by TSPSCs can change cells fate to become other types of cell, such that SSCs coculture with skin, prostate, and intestine mesenchyme transforms these cells from MSCs into epithelial cells fate.

MSCs in regenerative medicine: mesenchymal stem cells are CD73+, CD90+, CD105+, CD34, CD45, CD11b, CD14, CD19, and CD79a cells, also known as stromal cells. These bodily MSCs represented here do not account for MSCs of bone marrow and umbilical cord. Upon transplantation and transdifferentiation these bodily MSCs regenerate into cartilage, bones, and muscles tissue. Heart scar formed after heart attack and liver cirrhosis can be treated from MSCs. ECM coating provides the niche environment for MSCs to regenerate into hair follicle, stimulating hair growth.

UCSCs in regenerative medicine: umbilical cord, the readily available source of stem cells, has emerged as futuristic source for personalized stem cell therapy. Transplantation of UCSCs to Krabbe's disease patients regenerates myelin tissue and recovers neuroblastoma patients through restoring tissue homeostasis. The UCSCs organoids are readily available tissue source for treatment of neurodegenerative disease. Peritoneal fibrosis caused by long term dialysis, tendon tissue degeneration, and defective hyaline cartilage can be regenerated by UCSCs. Intravenous injection of UCSCs enables treatment of diabetes, spinal myelitis, systemic lupus erythematosus, Hodgkin's lymphoma, and congenital neuropathies. Cord blood stem cells banking avails long lasting source of stem cells for personalized therapy and regenerative medicine.

BMSCs in regenerative medicine: bone marrow, the soft sponge bone tissue that consisted of stromal, hematopoietic, and mesenchymal and progenitor stem cells, is responsible for blood formation. Even halo-HLA matched BMSCs can cure from disease and regenerate tissue. BMSCs can regenerate craniofacial tissue, brain tissue, diaphragm tissue, and liver tissue and restore erectile function and transdifferentiation monocytes. These multipotent stem cells can cure host from cancer and infection of HIV and HCV.

iPSCs in regenerative medicine: using the edge of iPSCs technology, skin fibroblasts and other adult tissues derived, terminally differentiated cells can be transformed into ESCs-like cells. It is possible that adult cells can be transformed into cells of distinct lineages bypassing the phase of pluripotency. The tissue specific defined culture can transform skin cells to become trophoblast, heart valve cells, photoreceptor cells, immune cells, melanocytes, and so forth. ECM complexation with iPSCs enables generation of tissue organoids for lung, kidney, brain, and other organs of the body. Similar to ESCs, iPSCs also can be transformed into cells representing three germ layers such as pacemaker cells and serotonin cells.

Stem cells in wildlife conservation: tissue biopsies obtained from dead and live wild animals can be either cryopreserved or transdifferentiated to other types of cells, through culture in defined culture medium or in vivo maturation. Stem cells and adult tissue derived iPSCs have great potential of regenerative medicine and disease therapeutics. Gonadal tissue procured from dead wild animals can be matured, ex vivo and in vivo for generation of sperm and egg, which can be used for assistive reproductive technology oriented captive breeding of wild animals or even for resurrection of wildlife.

Application of stem cells in regenerative medicine: stem cells (ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs) have diverse applications in tissue regeneration and disease therapeutics.

For the first time in 1998, Thomson isolated human ESCs (hESCs) [13]. ESCs are pluripotent in their nature and can give rise to more than 200 types of cells and promises for the treatment of any kinds of disease [13]. The pluripotency fate of ESCs is governed by functional dynamics of transcription factors OCT4, SOX2, NANOG, and so forth, which are termed as pluripotency factors. The two alleles of the OCT4 are held apart in pluripotency state in ESCs; phase through homologues pairing during embryogenesis and transdifferentiation processes [14] has been considered as critical regulatory switch for lineage commitment of ESCs. The diverse lineage commitment potential represents ESCs as ideal model for regenerative therapeutics of disease and tissue anomalies. This section of review on ESCs discusses transplantation and transdifferentiation of ESCs into retinal ganglion, hepatocytes, cardiomyocytes, pancreatic progenitors, chondrocytes, cones, egg sperm, and pacemaker cells (; ). Infection, cancer treatment, and accidents can cause spinal cord injuries (SCIs). The transplantation of hESCs to paraplegic or quadriplegic SCI patients improves body control, balance, sensation, and limbal movements [15], where transplanted stem cells do homing to injury sites. By birth, humans have fixed numbers of cone cells; degeneration of retinal pigment epithelium (RPE) of macula in central retina causes age-related macular degeneration (ARMD). The genomic incorporation of COCO gene (expressed during embryogenesis) in the developing embryo leads lineage commitment of ESCs into cone cells, through suppression of TGF, BMP, and Wnt signalling pathways. Transplantation of these cone cells to eye recovers individual from ARMD phenomenon, where transplanted cone cells migrate and form sheet-like structure in host retina [16]. However, establishment of missing neuronal connection of retinal ganglion cells (RGCs), cones, and PRE is the most challenging aspect of ARMD therapeutics. Recently, Donald Z Jacks group at John Hopkins University School of Medicine has generated RGCs from CRISPER-Cas9-m-Cherry reporter ESCs [17]. During ESCs transdifferentiation process, CRIPER-Cas9 directs the knock-in of m-Cherry reporter into 3UTR of BRN3B gene, which is specifically expressed in RGCs and can be used for purification of generated RGCs from other cells [17]. Furthermore, incorporation of forskolin in transdifferentiation regime boosts generation of RGCs. Coaxing of these RGCs into biomaterial scaffolds directs axonal differentiation of RGCs. Further modification in RGCs generation regime and composition of biomaterial scaffolds might enable restoration of vision for ARMD and glaucoma patients [17]. Globally, especially in India, cardiovascular problems are a more common cause of human death, where biomedical therapeutics require immediate restoration of heart functions for the very survival of the patient. Regeneration of cardiac tissue can be achieved by transplantation of cardiomyocytes, ESCs-derived cardiovascular progenitors, and bone marrow derived mononuclear cells (BMDMNCs); however healing by cardiomyocytes and progenitor cells is superior to BMDMNCs but mature cardiomyocytes have higher tissue healing potential, suppress heart arrhythmias, couple electromagnetically into hearts functions, and provide mechanical and electrical repair without any associated tumorigenic effects [18, 19]. Like CM differentiation, ESCs derived liver stem cells can be transformed into Cytp450-hepatocytes, mediating chemical modification and catabolism of toxic xenobiotic drugs [20]. Even today, availability and variability of functional hepatocytes are a major a challenge for testing drug toxicity [20]. Stimulation of ESCs and ex vivo VitK12 and lithocholic acid (a by-product of intestinal flora regulating drug metabolism during infancy) activates pregnane X receptor (PXR), CYP3A4, and CYP2C9, which leads to differentiation of ESCs into hepatocytes; those are functionally similar to primary hepatocytes, for their ability to produce albumin and apolipoprotein B100 [20]. These hepatocytes are excellent source for the endpoint screening of drugs for accurate prediction of clinical outcomes [20]. Generation of hepatic cells from ESCs can be achieved in multiple ways, as serum-free differentiation [21], chemical approaches [20, 22], and genetic transformation [23, 24]. These ESCs-derived hepatocytes are long lasting source for treatment of liver injuries and high throughput screening of drugs [20, 23, 24]. Transplantation of the inert biomaterial encapsulated hESCs-derived pancreatic progenitors (CD24+, CD49+, and CD133+) differentiates into -cells, minimizing high fat diet induced glycemic and obesity effects in mice [25] (). Addition of antidiabetic drugs into transdifferentiation regime can boost ESCs conservation into -cells [25], which theoretically can cure T2DM permanently [25]. ESCs can be differentiated directly into insulin secreting -cells (marked with GLUT2, INS1, GCK, and PDX1) which can be achieved through PDX1 mediated epigenetic reprogramming [26]. Globally, osteoarthritis affects millions of people and occurs when cartilage at joints wears away, causing stiffness of the joints. The available therapeutics for arthritis relieve symptoms but do not initiate reverse generation of cartilage. For young individuals and athletes replacement of joints is not feasible like old populations; in that case transplantation of stem cells represents an alternative for healing cartilage injuries [27]. Chondrocytes, the cartilage forming cells derived from hESC, embedded in fibrin gel effectively heal defective cartilage within 12 weeks, when transplanted to focal cartilage defects of knee joints in mice without any negative effect [27]. Transplanted chondrocytes form cell aggregates, positive for SOX9 and collagen II, and defined chondrocytes are active for more than 12wks at transplantation site, advocating clinical suitability of chondrocytes for treatment of cartilage lesions [27]. The integrity of ESCs to integrate and differentiate into electrophysiologically active cells provides a means for natural regulation of heart rhythm as biological pacemaker. Coaxing of ESCs into inert biomaterial as well as propagation in defined culture conditions leads to transdifferentiation of ESCs to become sinoatrial node (SAN) pacemaker cells (PCs) [28]. Genomic incorporation TBox3 into ESCs ex vivo leads to generation of PCs-like cells; those express activated leukocyte cells adhesion molecules (ALCAM) and exhibit similarity to PCs for gene expression and immune functions [28]. Transplantation of PCs can restore pacemaker functions of the ailing heart [28]. In summary, ESCs can be transdifferentiated into any kinds of cells representing three germ layers of the body, being most promising source of regenerative medicine for tissue regeneration and disease therapy (). Ethical concerns limit the applications of ESCs, where set guidelines need to be followed; in that case TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs can be explored as alternatives.

TSPSCs maintain tissue homeostasis through continuous cell division, but, unlike ESCs, TSPSCs retain stem cells plasticity and differentiation in tissue specific manner, giving rise to few types of cells (). The number of TSPSCs population to total cells population is too low; in that case their harvesting as well as in vitro manipulation is really a tricky task [29], to explore them for therapeutic scale. Human body has foundation from various types of TSPSCs; discussing the therapeutic application for all types is not feasible. This section of review discusses therapeutic application of pancreatic progenitor cells (PPCs), dental pulp stem cells (DPSCs), inner ear stem cells (IESCs), intestinal progenitor cells (IPCs), limbal progenitor stem cells (LPSCs), epithelial progenitor stem cells (EPSCs), mesoangioblasts (MABs), spermatogonial stem cells (SSCs), the skin derived precursors (SKPs), and adipose derived stem cells (AdSCs) (; ). During embryogenesis PPCs give rise to insulin-producing -cells. The differentiation of PPCs to become -cells is negatively regulated by insulin [30]. PPCs require active FGF and Notch signalling; growing more rapidly in community than in single cell populations advocates the functional importance of niche effect in self-renewal and transdifferentiation processes. In 3D-scaffold culture system, mice embryo derived PPCs grow into hollow organoid spheres; those finally differentiate into insulin-producing -cell clusters [29]. The DSPSCs, responsible for maintenance of teeth health status, can be sourced from apical papilla, deciduous teeth, dental follicle, and periodontal ligaments, have emerged as regenerative medicine candidate, and might be explored for treatment of various kinds of disease including restoration neurogenic functions in teeth [31, 32]. Expansion of DSPSCs in chemically defined neuronal culture medium transforms them into a mixed population of cholinergic, GABAergic, and glutaminergic neurons; those are known to respond towards acetylcholine, GABA, and glutamine stimulations in vivo. These transformed neuronal cells express nestin, glial fibrillary acidic protein (GFAP), III-tubulin, and voltage gated L-type Ca2+ channels [32]. However, absence of Na+ and K+ channels does not support spontaneous action potential generation, necessary for response generation against environmental stimulus. All together, these primordial neuronal stem cells have possible therapeutic potential for treatment of neurodental problems [32]. Sometimes, brain tumor chemotherapy can cause neurodegeneration mediated cognitive impairment, a condition known as chemobrain [33]. The intrahippocampal transplantation of human derived neuronal stem cells to cyclophosphamide behavioural decremented mice restores cognitive functions in a month time. Here the transplanted stem cells differentiate into neuronal and astroglial lineage, reduce neuroinflammation, and restore microglial functions [33]. Furthermore, transplantation of stem cells, followed by chemotherapy, directs pyramidal and granule-cell neurons of the gyrus and CA1 subfields of hippocampus which leads to reduction in spine and dendritic cell density in the brain. These findings suggest that transplantation of stem cells to cranium restores cognitive functions of the chemobrain [33]. The hair cells of the auditory system produced during development are not postmitotic; loss of hair cells cannot be replaced by inner ear stem cells, due to active state of the Notch signalling [34]. Stimulation of inner ear progenitors with -secretase inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY411575","term_id":"1257853995","term_text":"LY411575"}}LY411575) abrogates Notch signalling through activation of transcription factor atonal homologue 1 (Atoh1) and directs transdifferentiation of progenitors into cochlear hair cells [34]. Transplantation of in vitro generated hair cells restores acoustic functions in mice, which can be the potential regenerative medicine candidates for the treatment of deafness [34]. Generation of the hair cells also can be achieved through overexpression of -catenin and Atoh1 in Lrg5+ cells in vivo [35]. Similar to ear progenitors, intestine of the digestive tract also has its own tissue specific progenitor stem cells, mediating regeneration of the intestinal tissue [34, 36]. Dysregulation of the common stem cells signalling pathways, Notch/BMP/TGF-/Wnt, in the intestinal tissue leads to disease. Information on these signalling pathways [37] is critically important in designing therapeutics. Coaxing of the intestinal tissue specific progenitors with immune cells (macrophages), connective tissue cells (myofibroblasts), and probiotic bacteria into 3D-scaffolds of inert biomaterial, crafting biological environment, is suitable for differentiation of progenitors to occupy the crypt-villi structures into these scaffolds [36]. Omental implementation of these crypt-villi structures to dogs enhances intestinal mucosa through regeneration of goblet cells containing intestinal tissue [36]. These intestinal scaffolds are close approach for generation of implantable intestinal tissue, divested by infection, trauma, cancer, necrotizing enterocolitis (NEC), and so forth [36]. In vitro culture conditions cause differentiation of intestinal stem cells to become other types of cells, whereas incorporation of valproic acid and CHIR-99021 in culture conditions avoids differentiation of intestinal stem cells, enabling generation of indefinite pool of stem cells to be used for regenerative applications [38]. The limbal stem cells of the basal limbal epithelium, marked with ABCB5, are essential for regeneration and maintenance of corneal tissue [39]. Functional status of ABCB5 is critical for survival and functional integrity of limbal stem cells, protecting them from apoptotic cell death [39]. Limbal stem cells deficiency leads to replacement of corneal epithelium with visually dead conjunctival tissue, which can be contributed by burns, inflammation, and genetic factors [40]. Transplanted human cornea stem cells to mice regrown into fully functional human cornea, possibly supported by blood eye barrier phenomena, can be used for treatment of eye diseases, where regeneration of corneal tissue is critically required for vision restoration [39]. Muscle degenerative disease like duchenne muscular dystrophy (DMD) can cause extensive thrashing of muscle tissue, where tissue engineering technology can be deployed for functional restoration of tissue through regeneration [41]. Encapsulation of mouse or human derived MABs (engineered to express placental derived growth factor (PDGF)) into polyethylene glycol (PEG) fibrinogen hydrogel and their transplantation beneath the skin at ablated tibialis anterior form artificial muscles, which are functionally similar to those of normal tibialis anterior muscles [41]. The PDGF attracts various cell types of vasculogenic and neurogenic potential to the site of transplantation, supporting transdifferentiation of mesoangioblasts to become muscle fibrils [41]. The therapeutic application of MABs in skeletal muscle regeneration and other therapeutic outcomes has been reviewed by others [42]. One of the most important tissue specific stem cells, the male germline stem cells or spermatogonial stem cells (SSCs), produces spermatogenic lineage through mesenchymal and epithets cells [43] which itself creates niche effect on other cells. In vivo transplantation of SSCs with prostate, skin, and uterine mesenchyme leads to differentiation of these cells to become epithelia of the tissue of origin [43]. These newly formed tissues exhibit all physical and physiological characteristics of prostate and skin and the physical characteristics of prostate, skin, and uterus, express tissue specific markers, and suggest that factors secreted from SSCs lead to lineage conservation which defines the importance of niche effect in regenerative medicine [43]. According to an estimate, more than 100 million people are suffering from the condition of diabetic retinopathy, a progressive dropout of vascularisation in retina that leads to loss of vision [44]. The intravitreal injection of adipose derived stem cells (AdSCs) to the eye restores microvascular capillary bed in mice. The AdSCs from healthy donor produce higher amounts of vasoprotective factors compared to glycemic mice, enabling superior vascularisation [44]. However use of AdSCs for disease therapeutics needs further standardization for cell counts in dose of transplant and monitoring of therapeutic outcomes at population scale [44]. Apart from AdSCs, other kinds of stem cells also have therapeutic potential in regenerative medicine for treatment of eye defects, which has been reviewed by others [45]. Fallopian tubes, connecting ovaries to uterus, are the sites where fertilization of the egg takes place. Infection in fallopian tubes can lead to inflammation, tissue scarring, and closure of the fallopian tube which often leads to infertility and ectopic pregnancies. Fallopian is also the site where onset of ovarian cancer takes place. The studies on origin and etiology of ovarian cancer are restricted due to lack of technical advancement for culture of epithelial cells. The in vitro 3D organoid culture of clinically obtained fallopian tube epithelial cells retains their tissue specificity, keeps cells alive, which differentiate into typical ciliated and secretory cells of fallopian tube, and advocates that ectopic examination of fallopian tube in organoid culture settings might be the ideal approach for screening of cancer [46]. The sustained growth and differentiation of fallopian TSPSCs into fallopian tube organoid depend both on the active state of the Wnt and on paracrine Notch signalling [46]. Similar to fallopian tube stem cells, subcutaneous visceral tissue specific cardiac adipose (CA) derived stem cells (AdSCs) have the potential of differentiation into cardiovascular tissue [47]. Systemic infusion of CA-AdSCs into ischemic myocardium of mice regenerates heart tissue and improves cardiac function through differentiation to endothelial cells, vascular smooth cells, and cardiomyocytes and vascular smooth cells. The differentiation and heart regeneration potential of CA-AdSCs are higher than AdSCs [48], representing CA-AdSCs as potent regenerative medicine candidates for myocardial ischemic therapy [47]. The skin derived precursors (SKPs), the progenitors of dermal papilla/hair/hair sheath, give rise to multiple tissues of mesodermal and/or ectodermal origin such as neurons, Schwann cells, adipocytes, chondrocytes, and vascular smooth muscle cells (VSMCs). VSMCs mediate wound healing and angiogenesis process can be derived from human foreskin progenitor SKPs, suggesting that SKPs derived VSMCs are potential regenerative medicine candidates for wound healing and vasculature injuries treatments [49]. In summary, TSPSCs are potentiated with tissue regeneration, where advancement in organoid culture (; ) technologies defines the importance of niche effect in tissue regeneration and therapeutic outcomes of ex vivo expanded stem cells.

MSCs, the multilineage stem cells, differentiate only to tissue of mesodermal origin, which includes tendons, bone, cartilage, ligaments, muscles, and neurons [50]. MSCs are the cells which express combination of markers: CD73+, CD90+, CD105+, CD11b, CD14, CD19, CD34, CD45, CD79a, and HLA-DR, reviewed elsewhere [50]. The application of MSCs in regenerative medicine can be generalized from ongoing clinical trials, phasing through different state of completions, reviewed elsewhere [90]. This section of review outlines the most recent representative applications of MSCs (; ). The anatomical and physiological characteristics of both donor and receiver have equal impact on therapeutic outcomes. The bone marrow derived MSCs (BMDMSCs) from baboon are morphologically and phenotypically similar to those of bladder stem cells and can be used in regeneration of bladder tissue. The BMDMSCs (CD105+, CD73+, CD34, and CD45), expressing GFP reporter, coaxed with small intestinal submucosa (SIS) scaffolds, augment healing of degenerated bladder tissue within 10wks of the transplantation [51]. The combinatorial CD characterized MACs are functionally active at transplantation site, which suggests that CD characterization of donor MSCs yields superior regenerative outcomes [51]. MSCs also have potential to regenerate liver tissue and treat liver cirrhosis, reviewed elsewhere [91]. The regenerative medicinal application of MSCs utilizes cells in two formats as direct transplantation or first transdifferentiation and then transplantation; ex vivo transdifferentiation of MSCs deploys retroviral delivery system that can cause oncogenic effect on cells. Nonviral, NanoScript technology, comprising utility of transcription factors (TFs) functionalized gold nanoparticles, can target specific regulatory site in the genome effectively and direct differentiation of MSCs into another cell fate, depending on regime of TFs. For example, myogenic regulatory factor containing NanoScript-MRF differentiates the adipose tissue derived MSCs into muscle cells [92]. The multipotency characteristics represent MSCs as promising candidate for obtaining stable tissue constructs through coaxed 3D organoid culture; however heterogeneous distribution of MSCs slows down cell proliferation, rendering therapeutic applications of MSCs. Adopting two-step culture system for MSCs can yield homogeneous distribution of MSCs in biomaterial scaffolds. For example, fetal-MSCs coaxed in biomaterial when cultured first in rotating bioreactor followed with static culture lead to homogeneous distribution of MSCs in ECM components [7]. Occurrence of dental carries, periodontal disease, and tooth injury can impact individual's health, where bioengineering of teeth can be the alternative option. Coaxing of epithelial-MSCs with dental stem cells into synthetic polymer gives rise to mature teeth unit, which consisted of mature teeth and oral tissue, offering multiple regenerative therapeutics, reviewed elsewhere [52]. Like the tooth decay, both human and animals are prone to orthopedic injuries, affecting bones, joint, tendon, muscles, cartilage, and so forth. Although natural healing potential of bone is sufficient to heal the common injuries, severe trauma and tumor-recession can abrogate germinal potential of bone-forming stem cells. In vitro chondrogenic, osteogenic, and adipogenic potential of MSCs advocates therapeutic applications of MSCs in orthopedic injuries [53]. Seeding of MSCs, coaxed into biomaterial scaffolds, at defective bone tissue, regenerates defective bone tissues, within fourwks of transplantation; by the end of 32wks newly formed tissues integrate into old bone [54]. Osteoblasts, the bone-forming cells, have lesser actin cytoskeleton compared to adipocytes and MSCs. Treatment of MSCs with cytochalasin-D causes rapid transportation of G-actin, leading to osteogenic transformation of MSCs. Furthermore, injection of cytochalasin-D to mice tibia also promotes bone formation within a wk time frame [55]. The bone formation processes in mice, dog, and human are fundamentally similar, so outcomes of research on mice and dogs can be directional for regenerative application to human. Injection of MSCs to femur head of Legg-Calve-Perthes suffering dog heals the bone very fast and reduces the injury associated pain [55]. Degeneration of skeletal muscle and muscle cramps are very common to sledge dogs, animals, and individuals involved in adventurous athletics activities. Direct injection of adipose tissue derived MSCs to tear-site of semitendinosus muscle in dogs heals injuries much faster than traditional therapies [56]. Damage effect treatment for heart muscle regeneration is much more complex than regeneration of skeletal muscles, which needs high grade fine-tuned coordination of neurons with muscles. Coaxing of MSCs into alginate gel increases cell retention time that leads to releasing of tissue repairing factors in controlled manner. Transplantation of alginate encapsulated cells to mice heart reduces scar size and increases vascularisation, which leads to restoration of heart functions. Furthermore, transplanted MSCs face host inhospitable inflammatory immune responses and other mechanical forces at transplantation site, where encapsulation of cells keeps them away from all sorts of mechanical forces and enables sensing of host tissue microenvironment, and respond accordingly [57]. Ageing, disease, and medicine consumption can cause hair loss, known as alopecia. Although alopecia has no life threatening effects, emotional catchments can lead to psychological disturbance. The available treatments for alopecia include hair transplantation and use of drugs, where drugs are expensive to afford and generation of new hair follicle is challenging. Dermal papillary cells (DPCs), the specialized MSCs localized in hair follicle, are responsible for morphogenesis of hair follicle and hair cycling. The layer-by-layer coating of DPCs, called GAG coating, consists of coating of geletin as outer layer, middle layer of fibroblast growth factor 2 (FGF2) loaded alginate, and innermost layer of geletin. GAG coating creates tissue microenvironment for DPCs that can sustain immunological and mechanical obstacles, supporting generation of hair follicle. Transplantation of GAG-coated DPCs leads to abundant hair growth and maturation of hair follicle, where GAG coating serves as ECM, enhancing intrinsic therapeutic potential of DPCs [58]. During infection, the inflammatory cytokines secreted from host immune cells attract MSCs to the site of inflammation, which modulates inflammatory responses, representing MSCs as key candidate of regenerative medicine for infectious disease therapeutics. Coculture of macrophages (M) and adipose derived MSCs from Leishmania major (LM) susceptible and resistant mice demonstrates that AD-MSCs educate M against LM infection, differentially inducing M1 and M2 phenotype that represents AD-MSC as therapeutic agent for leishmanial therapy [93]. In summary, the multilineage differentiation potential of MSCs, as well as adoption of next-generation organoid culture system, avails MSCs as ideal regenerative medicine candidate.

Umbilical cord, generally thrown at the time of child birth, is the best known source for stem cells, procured in noninvasive manner, having lesser ethical constraints than ESCs. Umbilical cord is rich source of hematopoietic stem cells (HSCs) and MSCs, which possess enormous regeneration potential [94] (; ). The HSCs of cord blood are responsible for constant renewal of all types of blood cells and protective immune cells. The proliferation of HSCs is regulated by Musashi-2 protein mediated attenuation of Aryl hydrocarbon receptor (AHR) signalling in stem cells [95]. UCSCs can be cryopreserved at stem cells banks (; ), in operation by both private and public sector organization. Public stem cells banks operate on donation formats and perform rigorous screening for HLA typing and donated UCSCs remain available to anyone in need, whereas private stem cell banks operation is more personalized, availing cells according to donor consent. Stem cell banking is not so common, even in developed countries. Survey studies find that educated women are more eager to donate UCSCs, but willingness for donation decreases with subsequent deliveries, due to associated cost and safety concerns for preservation [96]. FDA has approved five HSCs for treatment of blood and other immunological complications [97]. The amniotic fluid, drawn during pregnancy for standard diagnostic purposes, is generally discarded without considering its vasculogenic potential. UCSCs are the best alternatives for those patients who lack donors with fully matched HLA typing for peripheral blood and PBMCs and bone marrow [98]. One major issue with UCSCs is number of cells in transplant, fewer cells in transplant require more time for engraftment to mature, and there are also risks of infection and mortality; in that case ex vivo propagation of UCSCs can meet the demand of desired outcomes. There are diverse protocols, available for ex vivo expansion of UCSCs, reviewed elsewhere [99]. Amniotic fluid stem cells (AFSCs), coaxed to fibrin (required for blood clotting, ECM interactions, wound healing, and angiogenesis) hydrogel and PEG supplemented with vascular endothelial growth factor (VEGF), give rise to vascularised tissue, when grafted to mice, suggesting that organoid cultures of UCSCs have promise for generation of biocompatible tissue patches, for treating infants born with congenital heart defects [59]. Retroviral integration of OCT4, KLF4, cMYC, and SOX2 transforms AFSCs into pluripotency stem cells known as AFiPSCs which can be directed to differentiate into extraembryonic trophoblast by BMP2 and BMP4 stimulation, which can be used for regeneration of placental tissues [60]. Wharton's jelly (WJ), the gelatinous substance inside umbilical cord, is rich in mucopolysaccharides, fibroblast, macrophages, and stem cells. The stem cells from UCB and WJ can be transdifferentiated into -cells. Homogeneous nature of WJ-SCs enables better differentiation into -cells; transplantation of these cells to streptozotocin induced diabetic mice efficiently brings glucose level to normal [7]. Easy access and expansion potential and plasticity to differentiate into multiple cell lineages represent WJ as an ideal candidate for regenerative medicine but cells viability changes with passages with maximum viable population at 5th-6th passages. So it is suggested to perform controlled expansion of WJ-MSCS for desired regenerative outcomes [9]. Study suggests that CD34+ expression leads to the best regenerative outcomes, with less chance of host-versus-graft rejection. In vitro expansion of UCSCs, in presence of StemRegenin-1 (SR-1), conditionally expands CD34+ cells [61]. In type I diabetic mellitus (T1DM), T-cell mediated autoimmune destruction of pancreatic -cells occurs, which has been considered as tough to treat. Transplantation of WJ-SCs to recent onset-T1DM patients restores pancreatic function, suggesting that WJ-MSCs are effective in regeneration of pancreatic tissue anomalies [62]. WJ-MSCs also have therapeutic importance for treatment of T2DM. A non-placebo controlled phase I/II clinical trial demonstrates that intravenous and intrapancreatic endovascular injection of WJ-MSCs to T2DM patients controls fasting glucose and glycated haemoglobin through improvement of -cells functions, evidenced by enhanced c-peptides and reduced inflammatory cytokines (IL-1 and IL-6) and T-cells counts [63]. Like diabetes, systematic lupus erythematosus (SLE) also can be treated with WJ-MSCs transplantation. During progression of SLE host immune system targets its own tissue leading to degeneration of renal, cardiovascular, neuronal, and musculoskeletal tissues. A non-placebo controlled follow-up study on 40 SLE patients demonstrates that intravenous infusion of WJ-MSC improves renal functions and decreases systematic lupus erythematosus disease activity index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), and repeated infusion of WJ-MSCs protects the patient from relapse of the disease [64]. Sometimes, host inflammatory immune responses can be detrimental for HSCs transplantation and blood transfusion procedures. Infusion of WJ-MSC to patients, who had allogenic HSCs transplantation, reduces haemorrhage inflammation (HI) of bladder, suggesting that WJ-MSCs are potential stem cells adjuvant in HSCs transplantation and blood transfusion based therapies [100]. Apart from WJ, umbilical cord perivascular space and cord vein are also rich source for obtaining MSCs. The perivascular MSCs of umbilical cord are more primitive than WJ-MSCs and other MSCs from cord suggest that perivascular MSCs might be used as alternatives for WJ-MSCs for regenerative therapeutics outcome [101]. Based on origin, MSCs exhibit differential in vitro and in vivo properties and advocate functional characterization of MSCs, prior to regenerative applications. Emerging evidence suggests that UCSCs can heal brain injuries, caused by neurodegenerative diseases like Alzheimer's, Krabbe's disease, and so forth. Krabbe's disease, the infantile lysosomal storage disease, occurs due to deficiency of myelin synthesizing enzyme (MSE), affecting brain development and cognitive functions. Progression of neurodegeneration finally leads to death of babies aged two. Investigation shows that healing of peripheral nervous system (PNS) and central nervous system (CNS) tissues with Krabbe's disease can be achieved by allogenic UCSCs. UCSCs transplantation to asymptomatic infants with subsequent monitoring for 46 years reveals that UCSCs recover babies from MSE deficiency, improving myelination and cognitive functions, compared to those of symptomatic babies. The survival rate of transplanted UCSCs in asymptomatic and symptomatic infants was 100% and 43%, respectively, suggesting that early diagnosis and timely treatment are critical for UCSCs acceptance for desired therapeutic outcomes. UCSCs are more primitive than BMSCs, so perfect HLA typing is not critically required, representing UCSCs as an excellent source for treatment of all the diseases involving lysosomal defects, like Krabbe's disease, hurler syndrome, adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Tay-Sachs disease (TSD), and Sandhoff disease [65]. Brain injuries often lead to cavities formation, which can be treated from neuronal parenchyma, generated ex vivo from UCSCs. Coaxing of UCSCs into human originated biodegradable matrix scaffold and in vitro expansion of cells in defined culture conditions lead to formation of neuronal organoids, within threewks' time frame. These organoids structurally resemble brain tissue and consisted of neuroblasts (GFAP+, Nestin+, and Ki67+) and immature stem cells (OCT4+ and SOX2+). The neuroblasts of these organoids further can be differentiated into mature neurons (MAP2+ and TUJ1+) [66]. Administration of high dose of drugs in divesting neuroblastoma therapeutics requires immediate restoration of hematopoiesis. Although BMSCs had been promising in restoration of hematopoiesis UCSCs are sparely used in clinical settings. A case study demonstrates that neuroblastoma patients who received autologous UCSCs survive without any associated side effects [12]. During radiation therapy of neoplasm, spinal cord myelitis can occur, although occurrence of myelitis is a rare event and usually such neurodegenerative complication of spinal cord occurs 624 years after exposure to radiations. Transplantation of allogenic UC-MSCs in laryngeal patients undergoing radiation therapy restores myelination [102]. For treatment of neurodegenerative disease like Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), traumatic brain injuries (TBI), Parkinson's, SCI, stroke, and so forth, distribution of transplanted UCSCs is critical for therapeutic outcomes. In mice and rat, injection of UCSCs and subsequent MRI scanning show that transplanted UCSCs migrate to CNS and multiple peripheral organs [67]. For immunomodulation of tumor cells disease recovery, transplantation of allogenic DCs is required. The CD11c+DCs, derived from UCB, are morphologically and phenotypically similar to those of peripheral blood derived CTLs-DCs, suggesting that UCB-DCs can be used for personalized medicine of cancer patient, in need for DCs transplantation [103]. Coculture of UCSCs with radiation exposed human lung fibroblast stops their transdifferentiation, which suggests that factors secreted from UCSCs may restore niche identity of fibroblast, if they are transplanted to lung after radiation therapy [104]. Tearing of shoulder cuff tendon can cause severe pain and functional disability, whereas ultrasound guided transplantation of UCB-MSCs in rabbit regenerates subscapularis tendon in fourwks' time frame, suggesting that UCB-MSCs are effective enough to treat tendons injuries when injected to focal points of tear-site [68]. Furthermore, transplantation of UCB-MSCs to chondral cartilage injuries site in pig knee along with HA hydrogel composite regenerates hyaline cartilage [69], suggesting that UCB-MSCs are effective regenerative medicine candidate for treating cartilage and ligament injuries. Physiologically circulatory systems of brain, placenta, and lungs are similar. Infusion of UCB-MSCs to preeclampsia (PE) induced hypertension mice reduces the endotoxic effect, suggesting that UC-MSCs are potential source for treatment of endotoxin induced hypertension during pregnancy, drug abuse, and other kinds of inflammatory shocks [105]. Transplantation of UCSCs to severe congenital neutropenia (SCN) patients restores neutrophils count from donor cells without any side effect, representing UCSCs as potential alternative for SCN therapy, when HLA matched bone marrow donors are not accessible [106]. In clinical settings, the success of myocardial infarction (MI) treatment depends on ageing, systemic inflammation in host, and processing of cells for infusion. Infusion of human hyaluronan hydrogel coaxed UCSCs in pigs induces angiogenesis, decreases scar area, improves cardiac function at preclinical level, and suggests that the same strategy might be effective for human [107]. In stem cells therapeutics, UCSCs transplantation can be either autologous or allogenic. Sometimes, the autologous UCSCs transplants cannot combat over tumor relapse, observed in Hodgkin's lymphoma (HL), which might require second dose transplantation of allogenic stem cells, but efficacy and tolerance of stem cells transplant need to be addressed, where tumor replace occurs. A case study demonstrates that second dose allogenic transplants of UCSCs effective for HL patients, who had heavy dose in prior transplant, increase the long term survival chances by 30% [10]. Patients undergoing long term peritoneal renal dialysis are prone to peritoneal fibrosis and can change peritoneal structure and failure of ultrafiltration processes. The intraperitoneal (IP) injection of WJ-MSCs prevents methylglyoxal induced programmed cell death and peritoneal wall thickening and fibrosis, suggesting that WJ-MSCs are effective in therapeutics of encapsulating peritoneal fibrosis [70]. In summary, UCB-HSCs, WJ-MSCs, perivascular MSCs, and UCB-MSCs have tissue regeneration potential.

Bone marrow found in soft spongy bones is responsible for formation of all peripheral blood and comprises hematopoietic stem cells (producing blood cells) and stromal cells (producing fat, cartilage, and bones) [108] (; ). Visually bone marrow has two types, red marrow (myeloid tissue; producing RBC, platelets, and most of WBC) and yellow marrow (producing fat cells and some WBC) [108]. Imbalance in marrow composition can culminate to the diseased condition. Since 1980, bone marrow transplantation is widely accepted for cancer therapeutics [109]. In order to avoid graft rejection, HLA typing of donors is a must, but completely matched donors are limited to family members, which hampers allogenic transplantation applications. Since matching of all HLA antigens is not critically required, in that case defining the critical antigens for haploidentical allogenic donor for patients, who cannot find fully matched donor, might relieve from donor constraints. Two-step administration of lymphoid and myeloid BMSCs from haploidentical donor to the patients of aplastic anaemia and haematological malignancies reconstructs host immune system and the outcomes are almost similar to fully matched transplants, which recommends that profiling of critically important HLA is sufficient for successful outcomes of BMSCs transplantation. Haploidentical HLA matching protocol is the major process for minorities and others who do not have access to matched donor [71]. Furthermore, antigen profiling is not the sole concern for BMSCs based therapeutics. For example, restriction of HIV1 (human immune deficiency virus) infection is not feasible through BMSCs transplantation because HIV1 infection is mediated through CD4+ receptors, chemokine CXC motif receptor 4 (CXCR4), and chemokine receptor 5 (CCR5) for infecting and propagating into T helper (Th), monocytes, macrophages, and dendritic cells (DCs). Genetic variation in CCR2 and CCR5 receptors is also a contributory factor; mediating protection against infection has been reviewed elsewhere [110]. Engineering of hematopoietic stem and progenitor cells (HSPCs) derived CD4+ cells to express HIV1 antagonistic RNA, specifically designed for targeting HIV1 genome, can restrict HIV1 infection, through immune elimination of latently infected CD4+ cells. A single dose infusion of genetically modified (GM), HIV1 resistant HSPCs can be the alternative of HIV1 retroviral therapy. In the present scenario stem cells source, patient selection, transplantation-conditioning regimen, and postinfusion follow-up studies are the major factors, which can limit application of HIV1 resistant GM-HSPCs (CD4+) cells application in AIDS therapy [72, 73]. Platelets, essential for blood clotting, are formed from megakaryocytes inside the bone marrow [74]. Due to infection, trauma, and cancer, there are chances of bone marrow failure. To an extent, spongy bone marrow microenvironment responsible for lineage commitment can be reconstructed ex vivo [75]. The ex vivo constructed 3D-scaffolds consisted of microtubule and silk sponge, flooded with chemically defined organ culture medium, which mimics bone marrow environment. The coculture of megakaryocytes and embryonic stem cells (ESCs) in this microenvironment leads to generation of functional platelets from megakaryocytes [75]. The ex vivo 3D-scaffolds of bone microenvironment can stride the path for generation of platelets in therapeutic quantities for regenerative medication of burns [75] and blood clotting associated defects. Accidents, traumatic injuries, and brain stroke can deplete neuronal stem cells (NSCs), responsible for generation of neurons, astrocytes, and oligodendrocytes. Brain does not repopulate NSCs and heal traumatic injuries itself and transplantation of BMSCs also can heal neurodegeneration alone. Lipoic acid (LA), a known pharmacological antioxidant compound used in treatment of diabetic and multiple sclerosis neuropathy when combined with BMSCs, induces neovascularisation at focal cerebral injuries, within 8wks of transplantation. Vascularisation further attracts microglia and induces their colonization into scaffold, which leads to differentiation of BMSCs to become brain tissue, within 16wks of transplantation. In this approach, healing of tissue directly depends on number of BMSCs in transplantation dose [76]. Dental caries and periodontal disease are common craniofacial disease, often requiring jaw bone reconstruction after removal of the teeth. Traditional therapy focuses on functional and structural restoration of oral tissue, bone, and teeth rather than biological restoration, but BMSCs based therapies promise for regeneration of craniofacial bone defects, enabling replacement of missing teeth in restored bones with dental implants. Bone marrow derived CD14+ and CD90+ stem and progenitor cells, termed as tissue repair cells (TRC), accelerate alveolar bone regeneration and reconstruction of jaw bone when transplanted in damaged craniofacial tissue, earlier to oral implants. Hence, TRC therapy reduces the need of secondary bone grafts, best suited for severe defects in oral bone, skin, and gum, resulting from trauma, disease, or birth defects [77]. Overall, HSCs have great value in regenerative medicine, where stem cells transplantation strategies explore importance of niche in tissue regeneration. Prior to transplantation of BMSCs, clearance of original niche from target tissue is necessary for generation of organoid and organs without host-versus-graft rejection events. Some genetic defects can lead to disorganization of niche, leading to developmental errors. Complementation with human blastocyst derived primary cells can restore niche function of pancreas in pigs and rats, which defines the concept for generation of clinical grade human pancreas in mice and pigs [111]. Similar to other organs, diaphragm also has its own niche. Congenital defects in diaphragm can affect diaphragm functions. In the present scenario functional restoration of congenital diaphragm defects by surgical repair has risk of reoccurrence of defects or incomplete restoration [8]. Decellularization of donor derived diaphragm offers a way for reconstruction of new and functionally compatible diaphragm through niche modulation. Tissue engineering technology based decellularization of diaphragm and simultaneous perfusion of bone marrow mesenchymal stem cells (BM-MSCs) facilitates regeneration of functional scaffolds of diaphragm tissues [8]. In vivo replacement of hemidiaphragm in rats with reseeded scaffolds possesses similar myography and spirometry as it has in vivo in donor rats. These scaffolds retaining natural architecture are devoid of immune cells, retaining intact extracellular matrix that supports adhesion, proliferation, and differentiation of seeded cells [8]. These findings suggest that cadaver obtained diaphragm, seeded with BM-MSCs, can be used for curing patients in need for restoration of diaphragm functions (; ). However, BMSCs are heterogeneous population, which might result in differential outcomes in clinical settings; however clonal expansion of BMSCs yields homogenous cells population for therapeutic application [8]. One study also finds that intracavernous delivery of single clone BMSCs can restore erectile function in diabetic mice [112] and the same strategy might be explored for adult human individuals. The infection of hepatitis C virus (HCV) can cause liver cirrhosis and degeneration of hepatic tissue. The intraparenchymal transplantation of bone marrow mononuclear cells (BMMNCs) into liver tissue decreases aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, CD34, and -SMA, suggesting that transplanted BMSCs restore hepatic functions through regeneration of hepatic tissues [113]. In order to meet the growing demand for stem cells transplantation therapy, donor encouragement is always required [8]. The stem cells donation procedure is very simple; with consent donor gets an injection of granulocyte-colony stimulating factor (G-CSF) that increases BMSCs population. Bone marrow collection is done from hip bone using syringe in 4-5hrs, requiring local anaesthesia and within a wk time frame donor gets recovered donation associated weakness.

The field of iPSCs technology and research is new to all other stem cells research, emerging in 2006 when, for the first time, Takahashi and Yamanaka generated ESCs-like cells through genetic incorporation of four factors, Sox2, Oct3/4, Klf4, and c-Myc, into skin fibroblast [3]. Due to extensive nuclear reprogramming, generated iPSCs are indistinguishable from ESCs, for their transcriptome profiling, epigenetic markings, and functional competence [3], but use of retrovirus in transdifferentiation approach has questioned iPSCs technology. Technological advancement has enabled generation of iPSCs from various kinds of adult cells phasing through ESCs or direct transdifferentiation. This section of review outlines most recent advancement in iPSC technology and regenerative applications (; ). Using the new edge of iPSCs technology, terminally differentiated skin cells directly can be transformed into kidney organoids [114], which are functionally and structurally similar to those of kidney tissue in vivo. Up to certain extent kidneys heal themselves; however natural regeneration potential cannot meet healing for severe injuries. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The procedure for generation of kidney organoids ex vivo, containing functional nephrons, has been identified for human. These ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. Such kidney organoids can serve as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However generation of fully functional kidneys is a far seen event with today's scientific technologies [114]. Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity [78]. The various approaches of iPSCs mediated retinal regeneration including ARMD have been reviewed elsewhere [79]. Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/ cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to haemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human [115]. Neurodegenerative disease like Alzheimer's and obstinate epilepsies can degenerate cerebrum, controlling excitatory and inhibitory signals of the brain. The inhibitory tones in cerebral cortex and hippocampus are accounted by -amino butyric acid secreting (GABAergic) interneurons (INs). Loss of these neurons often leads to progressive neurodegeneration. Genomic integration of Ascl1, Dlx5, Foxg1, and Lhx6 to mice and human fibroblast transforms these adult cells into GABAergic-INs (iGABA-INs). These cells have molecular signature of telencephalic INs, release GABA, and show inhibition to host granule neuronal activity [81]. Transplantation of these INs in developing embryo cures from genetic and acquired seizures, where transplanted cells disperse and mature into functional neuronal circuits as local INs [82]. Dorsomorphin and SB-431542 mediated inhibition of TGF- and BMP signalling direct transformation of human iPSCs into cortical spheroids. These cortical spheroids consisted of both peripheral and cortical neurons, surrounded by astrocytes, displaying transcription profiling and electrophysiology similarity with developing fetal brain and mature neurons, respectively [83]. The underlying complex biology and lack of clear etiology and genetic reprogramming and difficulty in recapitulation of brain development have barred understanding of pathophysiology of autism spectrum disorder (ASD) and schizophrenia. 3D organoid cultures of ASD patient derived iPSC generate miniature brain organoid, resembling fetal brain few months after gestation. The idiopathic conditions of these organoids are similar with brain of ASD patients; both possess higher inhibitory GABAergic neurons with imbalanced neuronal connection. Furthermore these organoids express forkhead Box G1 (FOXG1) much higher than normal brain tissue, which explains that FOXG1 might be the leading cause of ASD [84]. Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculosis and anticancer drugs [87]. The conventional multistep reprogramming for iPSCs consumes months of time, while CRISPER-Cas9 system based episomal reprogramming system that combines two steps together enables generation of ESCs-like cells in less than twowks, reducing the chances of culture associated genetic abrasions and unwanted epigenetic [80]. This approach can yield single step ESCs-like cells in more personalized way from adults with retinal degradation and infants with severe immunodeficiency, involving correction for genetic mutation of OCT4 and DNMT3B [80]. The iPSCs expressing anti-CCR5-RNA, which can be differentiated into HIV1 resistant macrophages, have applications in AIDS therapeutics [88]. The diversified immunotherapeutic application of iPSCs has been reviewed elsewhere [89]. The -1 antitrypsin deficiency (A1AD) encoded by serpin peptidase inhibitor clade A member 1 (SERPINA1) protein synthesized in liver protects lungs from neutrophils elastase, the enzyme causing disruption of lungs connective tissue. A1AD deficiency is common cause of both lung and liver disease like chronic obstructive pulmonary disease (COPD) and liver cirrhosis. Patient specific iPSCs from lung and liver cells might explain pathophysiology of A1AD deficiency. COPD patient derived iPSCs show sensitivity to toxic drugs which explains that actual patient might be sensitive in similar fashion. It is known that A1AD deficiency is caused by single base pair mutation and correction of this mutation fixes the A1AD deficiency in hepatic-iPSCs [85]. The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which are postmitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of Wnt signalling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions [116]. The iPSCs technology mediated somatic cell reprogramming of ventricular monocytes results in generation of cells, similar in morphology and functionality with PCs. SA note transplantation of PCs to large animals improves rhythmic heart functions. Pacemaker needs very reliable and robust performance so understanding of transformation process and site of transplantation are the critical aspect for therapeutic validation of iPSCs derived PCs [28]. Diabetes is a major health concern in modern world, and generation of -cells from adult tissue is challenging. Direct reprogramming of skin cells into pancreatic cells, bypassing pluripotency phase, can yield clinical grade -cells. This reprogramming strategy involves transformation of skin cells into definitive endodermal progenitors (cDE) and foregut like progenitor cells (cPF) intermediates and subsequent in vitro expansion of these intermediates to become pancreatic -cells (cPB). The first step is chemically complex and can be understood as nonepisomal reprogramming on day one with pluripotency factors (OCT4, SOX2, KLF4, and hair pin RNA against p53), then supplementation with GFs and chemical supplements on day seven (EGF, bFGF, CHIR, NECA, NaB, Par, and RG), and two weeks later (Activin-A, CHIR, NECA, NaB, and RG) yielding DE and cPF [86]. Transplantation of cPB yields into glucose stimulated secretion of insulin in diabetic mice defines that such cells can be explored for treatment of T1DM and T2DM in more personalized manner [86]. iPSCs represent underrated opportunities for drug industries and clinical research laboratories for development of therapeutics, but safety concerns might limit transplantation applications (; ) [117]. Transplantation of human iPSCs into mice gastrula leads to colonization and differentiation of cells into three germ layers, evidenced with clinical developmental fat measurements. The acceptance of human iPSCs by mice gastrula suggests that correct timing and appropriate reprogramming regime might delimit human mice species barrier. Using this fact of species barrier, generation of human organs in closely associated primates might be possible, which can be used for treatment of genetic factors governed disease at embryo level itself [118]. In summary, iPSCs are safe and effective for treatment of regenerative medicine.

The unstable growth of human population threatens the existence of wildlife, through overexploitation of natural habitats and illegal killing of wild animals, leading many species to face the fate of being endangered and go for extinction. For wildlife conservation, the concept of creation of frozen zoo involves preservation of gene pool and germ plasm from threatened and endangered species (). The frozen zoo tissue samples collection from dead or live animal can be DNA, sperms, eggs, embryos, gonads, skin, or any other tissue of the body [119]. Preserved tissue can be reprogrammed or transdifferentiated to become other types of tissues and cells, which opens an avenue for conservation of endangered species and resurrection of life (). The gonadal tissue from young individuals harbouring immature tissue can be matured in vivo and ex vivo for generation of functional gametes. Transplantation of SSCs to testis of male from the same different species can give rise to spermatozoa of donor cells [120], which might be used for IVF based captive breeding of wild animals. The most dangerous fact in wildlife conservation is low genetic diversity, too few reproductively capable animals which cannot maintain adequate genetic diversity in wild or captivity. Using the edge of iPSC technology, pluripotent stem cells can be generated from skin cells. For endangered drill, Mandrillus leucophaeus, and nearly extinct white rhinoceros, Ceratotherium simum cottoni, iPSC has been generated in 2011 [121]. The endangered animal drill (Mandrillus leucophaeus) is genetically very close to human and often suffers from diabetes, while rhinos are genetically far removed from other primates. The progress in iPSCs, from the human point of view, might be transformed for animal research for recapturing reproductive potential and health in wild animals. However, stem cells based interventions in wild animals are much more complex than classical conservation planning and biomedical research has to face. Conversion of iPSC into egg or sperm can open the door for generation of IVF based embryo; those might be transplanted in womb of live counterparts for propagation of population. Recently, iPSCs have been generated for snow leopard (Panthera uncia), native to mountain ranges of central Asia, which belongs to cat family; this breakthrough has raised the possibilities for cryopreservation of genetic material for future cloning and other assisted reproductive technology (ART) applications, for the conservation of cat species and biodiversity. Generation of leopard iPSCs has been achieved through retroviral-system based genomic integration of OCT4, SOX2, KLF4, cMYC, and NANOG. These iPSCs from snow leopard also open an avenue for further transformation of iPSCs into gametes [122]. The in vivo maturation of grafted tissue depends both on age and on hormonal status of donor tissue. These facts are equally applicable to accepting host. Ectopic xenografts of cryopreserved testis tissue from Indian spotted deer (Moschiola indica) to nude mice yielded generation of spermatocytes [123], suggesting that one-day procurement of functional sperm from premature tissue might become a general technique in wildlife conservation. In summary, tissue biopsies from dead or live animals can be used for generation of iPSCs and functional gametes; those can be used in assisted reproductive technology (ART) for wildlife conservation.

The spectacular progress in the field of stem cells research represents great scope of stem cells regenerative therapeutics. It can be estimated that by 2020 or so we will be able to produce wide array of tissue, organoid, and organs from adult stem cells. Inductions of pluripotency phenotypes in terminally differentiated adult cells have better therapeutic future than ESCs, due to least ethical constraints with adult cells. In the coming future, there might be new pharmaceutical compounds; those can activate tissue specific stem cells, promote stem cells to migrate to the side of tissue injury, and promote their differentiation to tissue specific cells. Except few countries, the ongoing financial and ethical hindrance on ESCs application in regenerative medicine have more chance for funding agencies to distribute funding for the least risky projects on UCSCs, BMSCs, and TSPSCs from biopsies. The existing stem cells therapeutics advancements are more experimental and high in cost; due to that application on broad scale is not feasible in current scenario. In the near future, the advancements of medical science presume using stem cells to treat cancer, muscles damage, autoimmune disease, and spinal cord injuries among a number of impairments and diseases. It is expected that stem cells therapies will bring considerable benefits to the patients suffering from wide range of injuries and disease. There is high optimism for use of BMSCs, TSPSCs, and iPSCs for treatment of various diseases to overcome the contradictions associated with ESCs. For advancement of translational application of stem cells, there is a need of clinical trials, which needs funding rejoinder from both public and private organizations. The critical evaluation of regulatory guidelines at each phase of clinical trial is a must to comprehend the success and efficacy in time frame.

Dr. Anuradha Reddy from Centre for Cellular and Molecular Biology Hyderabad and Mrs. Sarita Kumari from Department of Yoga Science, BU, Bhopal, India, are acknowledged for their critical suggestions and comments on paper.

There are no competing interests associated with this paper.

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Stem Cells Applications in Regenerative Medicine and ...

categoriaCardiac Stem Cells commentoComments Off on Stem Cells Applications in Regenerative Medicine and … dataDecember 23rd, 2021
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India Stem Cell Market speedy growth at US$ 1.27 Bn by 2028 with Thermofisher Scientific India, Pluristem Technologies, Becton Dickinson Private…

By daniellenierenberg

India Stem Cell Market to surpass huge revenue of USD 1.27 Billion at CAGR +13% by 2028.

Stem cell therapy in India helps in treating several diseases, including leukaemia, lymphoma, thalassemia, Parkinsons, Alzheimers, stroke, cerebral palsy, spinal cord injury, muscular dystrophy, etc. Stem cell therapy in India has shown promising results in India and as well as all over the world.

In comparison, in India it costs INR 10-20 lakh in private hospitals, while in government hospitals it is much cheaper INR 3-6 lakh depending on the type of procedure, he said

On average, private banking of stem cells derived from cord blood costs INR 50,000-70,000. Banks claim to freeze the cells in liquid nitrogen so that it can be used up to 20 years from the date of preservation.

Researchers hope stem cells will one day be effective in the treatment of many medical conditions and diseases. But unproven stem cell treatments can be unsafe so get all of the facts if youre considering any treatment. Stem cells have been called everything from cure-alls to miracle treatments.

Request a sample copy of report @ https://www.reportconsultant.com/request_sample.php?id=80360

Key players profiled in the report includes:

Thermofisher Scientific India Pvt. Ltd., Pluristem Technologies Ltd., Becton Dickinson Private Limited, Stem Cell Technologies India Pvt. Ltd., Merck Lifescience Pvt. Ltd., Cordlife India Pvt. Ltd., LifeCell International Pvt. Ltd., StemCyte India Therapeutics Private Limited, Stempeutics Research Private Limited, ReeLabs Private Limited, CryoSave, Indu Stem Cell Bank, Path Care Labs Pvt

The aim of the report is to equip relevant players in deciphering essential cues about the various real-time market based developments, also drawing significant references from historical data, to eventually present a highly effective market forecast and prediction, favoring sustainable stance and impeccable revenue flow despite challenges such as sudden pandemic, interrupted production and disrupted sales channel in the India Stem Cell market.

Market segments on the basis of:

This research report is an amalgamation of all relevant data pertaining to historic and current market specific information that systematically decide the future growth prospects of the India Stem Cell market. This section of the report further aims to enlighten report readers about the decisive developments and catastrophic implications caused by an unprecedented incident such as the pandemic that has visibly rendered unparalleled implications across the market.

This report is well documented to present crucial analytical review affecting the India Stem Cell market amidst COVID-19 outrage. The report is so designed to lend versatile understanding about various market influencers encompassing a thorough barrier analysis as well as an opportunity mapping that together decide the upcoming growth trajectory of the market. In the light of the lingering COVID-19 pandemic, this mindfully drafted research offering is in complete sync with the current ongoing market developments as well as challenges that together render tangible influence upon the holistic growth trajectory of the India Stem Cell market.

Besides presenting a discerning overview of the historical and current market specific developments, inclined to aid a future-ready business decision, this well-compiled research report on the India Stem Cell market also presents vital details on various industry best practices comprising SWOT and PESTEL analysis to adequately locate and maneuver profit scope. Therefore, to enable and influence a flawless market-specific business decision, aligning with the best industry practices, this specific research report on the market also lends a systematic rundown on vital growth triggering elements comprising market opportunities, persistent market obstacles and challenges, also featuring a comprehensive outlook of various drivers and threats that eventually influence the growth trajectory in the India Stem Cell market.

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India Stem Cell Geographical Segmentation Includes:

North America (U.S., Canada, Mexico)

Europe (U.K., France, Germany, Spain, Italy, Central & Eastern Europe, CIS)

Asia Pacific (China, Japan, South Korea, ASEAN, India, Rest of Asia Pacific)

Latin America (Brazil, Rest of L.A.)

Middle East and Africa (Turkey, GCC, Rest of Middle East)

Some Major TOC Points:

Chapter 1. Report Overview

Chapter 2. Growth Trends

Chapter 3. Market Share by Key Players

Chapter 4. Breakdown Data by Type and Application

Chapter 5. Market by End Users/Application

Chapter 6. COVID-19 Outbreak: India Stem Cell Industry Impact

Chapter 7. Opportunity Analysis in Covid-19 Crisis

Chapter 9. Market Driving Force

And More

In this latest research publication a thorough overview of the current market scenario has been portrayed, in a bid to aid market participants, stakeholders, research analysts, industry veterans and the like to borrow insightful cues from this ready-to-use market research report, thus influencing a definitive business discretion. The report in its subsequent sections also portrays a detailed overview of competition spectrum, profiling leading players and their mindful business decisions, influencing growth in the India Stem Cell market.

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Our research reports will give you the most realistic and incomparable experience of revolutionary market solutions. We have effectively steered business all over the world through our market research reports with our predictive nature and are exceptionally positioned to lead digital transformations. Thus, we craft greater value for clients by presenting progressive opportunities in the futuristic market.

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India Stem Cell Market speedy growth at US$ 1.27 Bn by 2028 with Thermofisher Scientific India, Pluristem Technologies, Becton Dickinson Private...

categoriaBone Marrow Stem Cells commentoComments Off on India Stem Cell Market speedy growth at US$ 1.27 Bn by 2028 with Thermofisher Scientific India, Pluristem Technologies, Becton Dickinson Private… dataFebruary 3rd, 2021
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Mobility Devices Market to Reach $14.86 Billion by 2026; Rising Incidence of Physical Disabilities Worldwide to Favor Growth of the Market: Fortune…

By daniellenierenberg

Pune, Feb. 03, 2020 (GLOBE NEWSWIRE) -- The global Mobility Devices Market size is projected to reach USD 14.86 billion by 2026, exhibiting a CAGR of 6.9% during the forecast period. Staggering rate of growth of geriatric population across the globe will be one of the crucial factors driving this market in the upcoming decade. Old age entails a plethora of disorders that generally restrict mobility in aged individuals and render them helpless. Given the rate at which the world population is ageing, the demand for devices aiding mobility is likely to spike. According the UNs Population Division, DESA, people at or above 60 years of age are currently numbered at 962 million. In the next three decades, the global geriatric population will reach 2.1 billion, predicts the DESA. Furthermore, old people are more susceptible to accidents associated deteriorating motor functions. For instance, the National Council of Aging estimates about 2.8 million aged Americans are rushed to hospital emergency rooms annually as a result of falling. Thus, a combination of aging and mishaps associated with the process will fuel the Mobility Devices Market trends during the forecast period.

For more information in the analysis of this report, visit: https://www.fortunebusinessinsights.com/industry-reports/mobility-devices-market-100520

Fortune Business Insights shares the above and other valuable market information in its recent report, titled Mobility Devices Market Size, Share & Industry Analysis, By Product (Wheelchairs, Mobility Scooters, Walking Aids, and Others); By End-user (Personal Users and Institutional Users); and Regional Forecast, 2019-2026, which states that the value of this market was at USD 8.75 billion in 2018. The report also provides:

Growing Aging Population and Rise in Mobility Impairment Disorders to Drive the Market

The older population around the globe is continuously growing at an unprecedented rate. Aging decreases the ability to move and reduces the ability to perform physical tasks to maintain independent functioning among the elderly population. The growing older population count is likely to increase the percentage usage of mobile devices during the forecast period. According to the World Health Organization (WHO), in 2017, the global population aged 60 years or over was around 962 million and is projected to reach about 2.1 billion by 2050. Rising prevalence of chronic conditions such as arthritis, cerebral palsy, and muscular dystrophy among every age group is expected to increase the demand for highly advanced mobility aid devices during the forecast period.

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North America to Lead the Pack; Europe to Follow Closely

Among regions, North America is set to dominate the Mobility Devices Market share owing to the rising prevalence mobility-related disorders in the region. Coupled with this is the increasing number of aged people in the region, which will propel the regional market.

Europe is anticipated to be the second most dominant region in this market on account of high proportion of aged people with mobility impairment. Asia-Pacific is touted to be the most promising region as geriatric population in the region is growing, while unmet needs of the people in Latin America, the Middle East, and Africa will create lucrative market opportunities.

Focus on Patient Safety and Comfort to Drive Innovation Among Players

Strengthening market position is expected to be the primary focus of key players in this market, says one of our lead analysts. One of the leading strategies adopted is increasing investment in innovation to come up with novel solutions, keeping patient comfort and safety in mind. Some players are also expanding their global presence through collaborations and acquisitions.

Industry Developments:

List of Top Players Profiled in the Mobility Devices Market Report:

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Detailed Table of Content:

TOC Continued.!

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Have a Look at Related Reports:

Wheelchair Market Size, Share & Industry Analysis, By Type (Manual & Powered), By Application (Standard Wheelchair, Bariatric Wheelchair, Sports Wheelchair, and Others) End-user (Personal User and Institutional User) and Regional Forecast, 2019-2026

Blood Pressure Monitoring Market Size, Share and Industry Analysis By Product Type (Sphygmomanometers, Digital Blood Pressure Monitors, Ambulatory Blood Pressure Monitors), By End User (Hospitals, Ambulatory Surgery Centers & Clinics, Home Healthcare & Others), and Regional Forecast 2018-2025

Advanced Wound Care Market Size, Share and Industry Analysis, By Product (Advanced Wound Dressings, Wound Care Devices & Active Wound Care), By Indication (Diabetic Foot Ulcers, Pressure Ulcers, Surgical Wounds, Others), By End User, and Regional Forecast 2018-2025

Magnetic Resonance Imaging (MRI) Systems Market Size, Share and Industry Analysis By Strength (Less than 1.5 T, 1.5 T & More than 1.5 T), By Application (Musculoskeletal, Neurology, Cardiology, Body Imaging), By End User (Hospitals, Ambulatory Surgical Centers, Diagnostic Centers), and Regional Forecast 2018-2025

Molecular Diagnostics Market Size, Share and Industry Analysis By Product Type (Instruments Reagents & Consumables), By Application (Infectious Disease, Blood Screening, Histology & Oncology), By Technique (Hospitals Amplification, Hybridization & Sequencing Techniques), End User (Hospitals, Clinical & Pathology Labs), and Regional Forecast 2018-2025

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Digital Radiography Market Size, Share and Global Trend By Product Type (Computed Radiography, Direct Digital Radiography), Application (General, Radiography Dentistry, Oncology, Orthopedic) End User (Hospital, Clinics, Diagnostic Centers) and Geography Forecast till 2026

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Cardiac Rhythm Management (CRM) Devices Market Size, Share and Global Trend Product By (Cardiac Pacemakers, Defibrillators, Cardiac Resynchronization Therapy Devices) By End User (Hospitals & Clinics, Ambulatory Surgery Centers), and Geography Forecast to 2026

Transrectal Ultrasound (TRUS) Market Size, Share and Industry Analysis By Product (Systems, Transducers), Type (Cart/Trolley Based, Portable), Application (Diagnostic, Image-guided Treatment), End User (Diagnostic Laboratories, Hospitals) and Regional Forecast, 2018 - 2025

Orthobiologics Market Size, Share and Industry Analysis by Product Type (Viscosupplements, Bone Growth Stimulators, Demineralized Bone Matrix, Synthetic Bone Substitutes, Stem Cells, Allografts), By Application (Spinal Fusion, Maxillofacial & Dental, Soft Tissue Repair, Reconstructive & Fracture Surgery), By End User (Hospitals, Ambulatory Surgical Centers, Speciality Clinics), and Regional Forecast 2019-2026

Dental Implants Market Size, Share and Industry Analysis By Material (Titanium Implants, Zirconium Implants), By Type (Endosteal Implants, Subperiosteal Implants, Transosteal Implants), By Design (Tapered Implants, Parallel Implants), By End-user (Hospitals, Dental Clinics, Academic & Research Institutes) and Regional Forecast, 2019 2026

Immunodiagnostics Market Size, Share and Industry Analysis By Product Instruments, Reagents & Consumables), By Application (Oncology & Endocrinology, Hepatitis & Retrovirus, Cardiac Markers, Infectious Diseases), By End user (Clinical Laboratories, Hospitals, Physicians Offices), By End-user(Hospitals, Dental Clinics, Academic & Research Institutes) and Regional Forecast, 2019 2026

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Mobility Devices Market to Reach $14.86 Billion by 2026; Rising Incidence of Physical Disabilities Worldwide to Favor Growth of the Market: Fortune...

categoriaCardiac Stem Cells commentoComments Off on Mobility Devices Market to Reach $14.86 Billion by 2026; Rising Incidence of Physical Disabilities Worldwide to Favor Growth of the Market: Fortune… dataFebruary 3rd, 2020
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Psychiatric body condemns use of stem cell therapies to treat psychiatric disorders – Moneycontrol.com

By daniellenierenberg

The Indian Psychiatric Society (IPS) the professional body that represents psychiatrists in India, strongly condemned the use of stem cell therapy in psychiatric disorders, particularly autism, until such a time that research evidence substantiated its effectiveness.

IPS, in its position statement on stem cell therapy on January 17, said that till now, there is no scientifically validated and scrutinized research evidence that proves that stem cells are helpful in any psychiatric disorders including autism.

Autism is a complex neurodevelopmental disorder with no known single cause.

The advisory from the IPS comes at a time when stem cell therapy clinics that claim to have developed stem cell therapies to treat complex psychiatric problems such as autism, cerebral palsy (movement disorder), muscular dystrophy (weakness of muscles), mental retardation, spinal cord injury and brain stroke have mushroomed across the country.

These stem cell therapy centres extract stem cells from the bone marrow of each child and then inject it into the childs spinal canal. The whole procedure takes place under general anaesthesia.

These clinics use aggressive marketing techniques and false claims to lure parents of children who are suffering from disease like autism.

The Indian Council of Medical Research (ICMR) has already published guidelines that cover the various diseases that are applicable for stem cell treatment. No psychiatric disorders, including autism, are listed there under this advisory.

Stem cells are special human cells that have the ability to develop into many different cell types, from muscle cells to brain cells. In some cases, they also have the potential to repair damaged tissues, and provide a cure for various diseases. But the clinical evidence at this point is low.

Psychiatric disorders including autism are combined derangements of both neurodevelopmental and neurodegenerative trajectories of brain and are polygenetic in origin. So they actually are symptomatic manifestations of a variety of different pathogenetic processes about which scientific evidence is as yet inconclusive, IPS said.

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Psychiatric body condemns use of stem cell therapies to treat psychiatric disorders - Moneycontrol.com

categoriaIPS Cell Therapy commentoComments Off on Psychiatric body condemns use of stem cell therapies to treat psychiatric disorders – Moneycontrol.com dataJanuary 20th, 2020
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2019: the year gene therapy came of age – Times of India

By daniellenierenberg

WASHINGTON: In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering - by editing her genome.Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research - gene therapy.'; var randomNumber = Math.random(); var isIndia = (window.geoinfo && window.geoinfo.CountryCode === 'IN') && (window.location.href.indexOf('outsideindia') === -1 ); console.log(isIndia && randomNumber "I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness - stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 - pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies - bringing the total to eight - approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million - meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion - and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal - and his excommunication from the scientific community - when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species - malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

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2019: the year gene therapy came of age - Times of India

categoriaBone Marrow Stem Cells commentoComments Off on 2019: the year gene therapy came of age – Times of India dataDecember 27th, 2019
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A #ReUp of 2019: The year when gene therapy, DNA modifications came of age & saved lives – Economic Times

By daniellenierenberg

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

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6 Nov, 2019

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Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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A #ReUp of 2019: The year when gene therapy, DNA modifications came of age & saved lives - Economic Times

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In a first, 26-year-old DMD patient in UP survives with stem cell therapy – India TV News

By daniellenierenberg

Image Source : PTI

Children, suffering from DMD, usually die of cardio-respiratory failure. Represtational image

Duchenne Muscular Dystrophy (DMD) is a deadly genetic disorder, 99.9 per cent people suffering from which, die between the age of 13 to 23 years. However, in a first, a 26-year-old patient from Lucknow has survived DMD by regularly taking stem cells for the last five years.

Children, suffering from DMD, usually die of cardio-respiratory failure. But with the stem cell therapy, this patient has not lost muscle power in last five years and heart and lung muscles and the upper half of the body are working well.

Dr. B.S Rajput, the surgeon who is treating this patient, said, "DMD is a type of muscular dystrophy and being a genetic disorder, it is very difficult to treat. Autologous (from your own body) bone marrow cell transplant or stem cell therapy in such cases was started in Mumbai about 10 years back.

Dr Rajput, who was recently appointed as visiting professor at GSVM Medical College, Kanpur, said he has treated several hundred DMD patients and recently this combination protocol was published in the international Journal of Embryology and stem cell research.

The patient's father is elated that his son has maintained well with this treatment and now has even started earning by working on computers.

According to Dr Rajput, this disease is endemic in eastern UP, especially Azamgarh, Jaunpur, Ballia and some of the adjoining districts of Bihar, and one out of every 3,500 male child, suffers from the disease.

Yet the disease is not given as much attention as it should be.

Dr Rajput, who is consultant bone cancer and stem cell transplant surgeon from Mumbai, said though patients in Uttar Pradesh and Bihar get financial support from the Chief Minister's Relief Funds, the treatment of autologous bone marrow cell transplant is not included in the package list of Ayushman Bharat scheme, which deprives many from getting the treatment.

The doctor further informed that efforts are being made to establish the department of regenerative medicine in the medical college, where bone marrow cell transplant and stem cell therapy would be done even for other intractable problems like spinal cord injury, arthritis knee and motor neurone disease.

ALSO READ |Fasting triggers regeneration of stem cells capacity: Study

ALSO READ |UK patient 'free' of HIV after stem cell treatment

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In a first, 26-year-old DMD patient in UP survives with stem cell therapy - India TV News

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In a first, 26-yr-old DMD patient in UP survives with stem cell therapy – Outlook India

By daniellenierenberg

In a first, 26-yr-old DMD patient in UP survives with stem cell therapy

Lucknow, Oct 22 (IANS) Duchenne Muscular Dystrophy (DMD) is a deadly genetic disorder, 99.9 per cent people suffering from which, die between the age of 13 to 23 years. However, in a first, a 26-year-old patient from Lucknow has survived DMD by regularly taking stem cells for the last five years.

Children, suffering from DMD, usually die of cardio-respiratory failure. But with the stem cell therapy, this patient has not lost muscle power in last five years and heart and lung muscles and the upper half of the body are working well.

Dr. B.S Rajput, the surgeon who is treating this patient, said, "DMD is a type of muscular dystrophy and being a genetic disorder, it is very difficult to treat. Autologous (from your own body) bone marrow cell transplant or stem cell therapy in such cases was started in Mumbai about 10 years back.

Dr Rajput, who was recently appointed as visiting professor at GSVM Medical College, Kanpur, said he has treated several hundred DMD patients and recently this combination protocol was published in the international Journal of Embryology and stem cell research.

The patient''s father is elated that his son has maintained well with this treatment and now has even started earning by working on computers.

According to Dr Rajput, this disease is endemic in eastern UP, especially Azamgarh, Jaunpur, Ballia and some of the adjoining districts of Bihar, and one out of every 3,500 male child, suffers from the disease.

Yet the disease is not given as much attention as it should be.

Dr Rajput, who is consultant bone cancer and stem cell transplant surgeon from Mumbai, said though patients in Uttar Pradesh and Bihar get financial support from the Chief Minister''s Relief Funds, the treatment of autologous bone marrow cell transplant is not included in the package list of Ayushman Bharat scheme, which deprives many from getting the treatment.

The doctor further informed that efforts are being made to establish the department of regenerative medicine in the medical college, where bone marrow cell transplant and stem cell therapy would be done even for other intractable problems like spinal cord injury, arthritis knee and motor neurone disease.

--IANS

amita/rtp

Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: IANS

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In a first, 26-yr-old DMD patient in UP survives with stem cell therapy - Outlook India

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Lucknow: In a first, 26-yr-old DMD patient in UP survives with stem cell therapy – ETHealthworld.com

By daniellenierenberg

Lucknow: Duchenne Muscular Dystrophy (DMD) is a deadly genetic disorder, 99.9 per cent people suffering from which, die between the age of 13 to 23 years. However, in a first, a 26-year-old patient from Lucknow has survived DMD by regularly taking stem cells for the last five years.

Children, suffering from DMD, usually die of cardio-respiratory failure. But with the stem cell therapy, this patient has not lost muscle power in last five years and heart and lung muscles and the upper half of the body are working well.

Dr. B.S Rajput, the surgeon who is treating this patient, said, "DMD is a type of muscular dystrophy and being a genetic disorder, it is very difficult to treat. Autologous (from your own body) bone marrow cell transplant or stem cell therapy in such cases was started in Mumbai about 10 years back.

Dr Rajput, who was recently appointed as visiting professor at GSVM Medical College, Kanpur, said he has treated several hundred DMD patients and recently this combination protocol was published in the international Journal of Embryology and stem cell research.

According to Dr Rajput, this disease is endemic in eastern UP, especially Azamgarh, Jaunpur, Ballia and some of the adjoining districts of Bihar, and one out of every 3,500 male child, suffers from the disease.

Yet the disease is not given as much attention as it should be.

Dr Rajput, who is consultant bone cancer and stem cell transplant surgeon from Mumbai, said though patients in Uttar Pradesh and Bihar get financial support from the Chief Minister's Relief Funds, the treatment of autologous bone marrow cell transplant is not included in the package list of Ayushman Bharat scheme, which deprives many from getting the treatment.

The doctor further informed that efforts are being made to establish the department of regenerative medicine in the medical college, where bone marrow cell transplant and stem cell therapy would be done even for other intractable problems like spinal cord injury, arthritis knee and motor neurone disease.

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Lucknow: In a first, 26-yr-old DMD patient in UP survives with stem cell therapy - ETHealthworld.com

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Stem cells treatment gives hope in fighting Autism, blood disorders – OrissaPOST

By daniellenierenberg

Bhubaneswar: The advanced treatment of using stem cells for treating Autism and other neurological ailments have come as a ray of hope for the people living with some of these ailments. Medical experts working in the sector claim that the use of the technology improved the lives of many.

According to experts who practice stem cell therapy, the results have been overwhelming. Many of the patients have either been able to fight a deadly disease with the help of stem cells while many have been able to improve their quality of lives by using it. However, the technology is still not used widely in state hospitals.

Medical experts claim that stem cells could be used to treat neurological disorders like Autism, cerebral palsy, mental retardation, brain stroke, muscular dystrophy, spinal cord injury, head injury, cerebellar ataxia, dementia, motor neurone disease, multiple sclerosis while it has also been used to treat cancers like blood cancer with the help of bone marrow transplant when assisted by stem cell therapy.

However, treatment of Autism with stem cells is a new developing sector where visible changes are said to have been reported among children treated with this technology. However, the advanced technology which is now confined to only private sector is a bit expensive.

Autistic kids are usually treated with drugs for symptomatic relief, special education, occupational speech and behavioural therapies. In Autism, despite the best available medical and rehabilitative treatments satisfactory relief is still a far cry, said Dr Nandini Gokulchandran, Head Medical Services, NeuroGen Brain and Spine Institute, Mumbai.

Dr Gokulchandran claims that she has treated many cases of Autism in kids with stem cells which helped in overcoming their limited abilities. Under the treatment regime, an insertion procedure is undertaken followed by training to improve the skills and abilities of autistic kids.

Another neurologist, Dr Richa Bansod said that in India it has been reported that 1 in every 250 children have Autism and this number in increasing with better recognition and awareness of the condition. On the other hand, stem cells are now been used to fight deadly diseases.

Dr Joydeep Chakaborty, an oncologist and stem cell expert from HCG Cancer Hospital, Kolkata said, Stem cells and bone marrow transplants are now being used to cure blood cancer in many cases. It is also widely used to treat blood disorders like Thalassemia, Sickle Cell Anaemia and others.

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Stem cells treatment gives hope in fighting Autism, blood disorders - OrissaPOST

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Stem Cell Therapy in India – Stem Cell Treatment in Delhi …

By Dr. Matthew Watson

"Stem Cell Cure Pvt. Ltd." is one of the most trusted and highlighted company in India which has expertise in providing best Stem Cell Services (for Blood disorders) in top most hospital of India for all major degenerative diseases. Our company is providing advanced medical treatment in India which applies in case of all other medical treatment fail to cure non-treatable diseases. We provide our services through some medical devices such as bone marrow aspiration concentrate (BMAC) kit, platelet rich plasma (PRP) kit, stem cell banking and stem cells services (isolated from bone marrow, placenta and adipose) for research/clinical trial purpose only.We are providing advanced medical treatment in India where all other medical treatment fail then this stem cell treatment apply to cure such non-treatable diseases.

It is the single channel that has comprehensive stem cell treatment and other medical treatment protocols and employs stem cells in different form as per the requirement of best suite on the basis of degenerative disease application. Stem cell therapy is helpful to treat many blood disorder such as thalassemia, sickle cell anemia, leukemia, aplastic anemia and other organ related disorder such as muscular dystrophy, spinal cord Injury, diabetes, chronic kidney disease (CKD), cerebral palsy, autism, optic nerve atrophy, retinitis pigmentosa, lung (COPD) disease and liver cirrhosis and our list of services doesn't end here.

"Stem Cell Cure" company is working with some India's top stem cell therapy centers, cord blood stem cell preservation banks and approved stem cell research labs to explore and share their unique stem cell solutions with our best services via coordinating of our clinician and researcher and solving every type of patient queries regarding stem cell therapy.

Our company is providing best medical treatment in India and also has expertization in stem cell therapy and for the needed patients in all those application which can treat by stem cell therapy. We have stem cells in different forms to make the better recovery of patient and refer the best stem cell solutions after the evaluation of patient case study by our experts. Our experts in this field work together with patients though the collaborative patient experience to give you greater peace of mind to develop clear evidence based path. We have highly experts in our team and our experts are strong in research and clinical research from both points of view.

Our mission is to provide best stem cell therapy at reasonable price not only in India but also throughout the whole world so that every needed patients can get best stem cell therapy to improve his life.

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Stem Cell Therapy in India - Stem Cell Treatment in Delhi ...

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Stem cell therapy: proffering hope for special needs patients … – BusinessDay (satire) (press release) (registration) (blog)

By JoanneRUSSELL25

Hope is surely on the way for children with special needs as Alok Sharma, a world renowned neurosurgeon, Neuroscientist and professor, a director of NeuroGen Brain and Spine Institute India visited Nigeria recently to shed light on the efficacy of stem cells in treating children with special needs.With over 5000 patients treated from 50 countries, 68 scientific papers and 14 published books, and an overall 91% success rate, Alok was determined to enlighten participants who attended the one day seminar on stem cell awareness and its importance.According to Asok, We are the pioneers of introduction to Stem Cell Therapy for neurological disorders. We make use of holistic, comprehensive approach to treat our patients with a combination of stem cell therapy and neuro-rehabilitation. We use adult stem cells derived from the patients own bone marrow, as they are the safest and most feasible type of cells. Since every patient is different, our treatment protocol is customised according to the patients requirements.We now have a treatment that is very effective and a large number of people can benefit from this. The old thinking was that when the central nervous system is damaged then it is beyond repairs but the new thinking is that some degree of repair is possible. Stem cells have three capabilities. They repair, regenerate or replaced. It took us between seven to eight years to prove that stem cells can convert to nerve cells and when we became very sure, we went on to use on humans and the results have been outstanding He said.Asked who can be treated with the stem cell procedure and Asok says for paediatric, we treat children with autism, cerebral palsy, intellectual disability and muscular dystrophy. For adults, we treat spinal cord injury, stroke, traumatic brain injury/head injury, motor neuro disease/amyotrophic lateral scierosis and other neurological disorders.Asok explains that there are many types of stem cells used, but broadly they can be classified into 3 types:-Embryonic stem cells: Embryonic stem cells, as their name suggests, are derived from 3-4 day embryos. These are obtained from spare embryos from IVF clinics with the consent of the donor. During this early developmental period, the cells that will ultimately give rise to the developing fetus can be encouraged to develop into tissues of different origins (totipotency) contributing greatly to stem cell therapy. However, there are many ethical and medical issues regarding its use. These are therefore, not being used presently.Umbilical cord stem cells: These cells are derived from the umbilical cord which connects the baby and the mother at birth. Stem cells derived from the umbilical cord are stored by various cord blood banking companies. These stem cells do not have any major ethical issues surrounding their usage, but availability can be a problem.Adult stem cells: They can be derived from the same patient, from either the hip bone or the adipose/fat tissue. Currently, they are the most popularly used stem cells. The benefits that adult stem cells offer are:1, They are available in abundance and can be isolated easily.2, They are isolated from patients, which overcomes the problem of immunological rejection.3, Adult stem cells have the potential to replenish many specialized cells from just a few unspecialized ones.4, They do not have any ethical issues as they do not involve destruction of embryos.5, The risk of tumor formation is greatly reduced as compared to the use of embryonic stem cells.There are fears about stem cell therapy but Asok cleared the air when he said this isnt the truth as the one feared is the embryonic stem cells (ESCs) which are stem cells derived from the undifferentiated inner mass cells of a human embryo. ESCs are just one of the types of stem cells but we do not make use of that in our hospital as explained earlier, we use Adult Stem Cells. We do not use the embryotic stem cells because they have the tendency to become tumours in the body. He explained.On how the procedure works, he says a thin needle is inserted into the hip bone to pull the marrow out. The procedure takes between 15 to 30 minutes. The patient is then sent back to the room for about 3 to 4 hours to rest for the next procedureon same day, within the 2 to 4 hours, the stem cells are separated and purified in their stem cell laboratory by using density gradient centrifugation. Once the stem cells have been purified, the patient is taken back to the operation theatre and the stem cells are injected into the spinal space. In some patients, for instance, patients with muscular dystrophy, the stem cells are diluted and injected into the muscles using a very thin needle.One of the participants at the seminar, Marvis Isokpehi, whose child is autistic, had this to say I am glad I came for this seminar. Initially, we were told anything that has to do with brain damage cannot be cured or improved only managed but we see that God helping the scientist, things are getting better. My child was diagnosed by 2. She walked at 17 months, sat at 8 months and she only babbled. She could use her hands and able to put things in her mouth herself but later, the growth began to drop and along the line, I took up the challenge and went back to school to learn about taking care of her and also to help others. I went to Federal College of Education (special) Oyo and specialised in Education for the intellectually disabled. Said Marvis.For Akhere Akran, the Manager of Agatha Obiageli Aghedo Memorial Foundation and participant, one of the arms of our foundation aimed at helping to lessen the burden of the less privileged in the community is the St Agatha Children Centre, where we advocate for children with special needs. I am glad I will be going back to let the parents of these children know there is hope and I am trusting God for funds because that is truly the core of everything. I appeal to the government to fund this and encourage private organisations to help reduce the cost of this treatment to the barest minimum. Its high time we stop stigmatisation or thinking its a result of the mothers past life of the fathers mistakes. It is a medical situation that needs medical attention. Akran expressed.Andelene Thysse is a director at Stem Cell Africa and she helped facilitate the seminar and for her, it is high time Nigeria gets involved We are currently looking at establishing a stem centre at Mozambique. I would have loved that we establish in Nigeria because Nigeria is closer to everything but since we arent getting the audience required, we are going to other African countries interested. Going to NeuroGen Institute for treatment per patient costs about $11,000 imagine if Nigeria has the facility, the price can slash down to $6,000 or even below Andelene stated.Shedding more light on costing, Asok says If we are to set up such a facility in an existing hospital, the cost of setting it up is $US500, 000 and I am assuming all facilities are functioning already. If we have to set up as a whole which includes getting land and building, it will be more expensive. This may sound expensive but it is worth it because it will save you the stress for the future. More important than the money is the permission from the government of the country. The government has to give us the permission because it is what is happening in other African countries. We have had good response and cooperation from government in Kenya, South Africa and Zimbabwe. We have quite a number of Nigerians who come to us in India for this treatment. We treat 50 patients from around the world per week about 5-10 are from Africa and Nigeria is among this percentage.

Kemi Ajumobi

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Stem cell therapy: proffering hope for special needs patients ... - BusinessDay (satire) (press release) (registration) (blog)

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Three Bangladeshi patients undergo stem cell therapy in Mumbai – India Today

By NEVAGiles23

Mumbai, Apr 4 (PTI) Three Bangladeshi patients, suffering from an incurable muscular dystrophy, today underwent first stem cell therapy at a Navi Mumbai based treatment centre.

"We applied a simple therapy to the patients. We took out the stem cells from their bone marrow in the hip bone and after the required processing we injected it back into their body.

"We will wait for the results as to how they respond to such treatment. Meanwhile, physiotherapy and occupational therapy is being offered to them as well," Avantika Patil, coordinator between the patients and the treating centre told PTI.

Patil, is part of the team of NeuroGen, a brain and spine institute that keeps the track of its patients.

"We learnt about the patients through an article in an international newspaper and decided to contact them as we specialise in treating such diseases.

"I am also in contact with one Noor Khan from Bangladesh, an activist who helped the three patients to furnish documents and visa procedures," she said.

A Mumbai-based organisation specialising in such diseases, Meditourz, in collaboration with NeuroGen based in Navi Mumbai, offered to provide treatment to them.

The trio have been suffering from a rare disease Duchenne Muscular Dystrophy since their birth. This is a genetic disorder which causes progressive muscle degeneration and patients rarely live beyond 30 years of age, Patil said.

Among the three, Shorab (8 year old) is having a mild disorder and early medical intervention will definitely help in terms of less painful life. Compared to him, the disease is progressive in other two patients, she said.

Tofazzal Hossain, a fruit vendor from rural Meherpur in Bangladesh, had sought mercy killing for his sons - Abdus (24) and Rahinul (14) - and grandson Shorab from his government as he could not afford the cost of their treatment.

The Navi Mumbai based centre approached the three patients through Indian government and expressed willingness to provide treatment to the disease.

Air India also offered free round trip tickets to the six persons -- three patients and three caretakers accompanying them to Mumbai from Kolkata following an appeal from Alok Sharma, neurosurgeon at the NeuroGen.

"The three patients and the three persons accompanying them took this evenings Air India flight from Kolkata to Mumbai and will also return by an Air India flight after treatment - entirely free of any charges," Air India said in a statement. PTI ND RMT

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Three Bangladeshi patients undergo stem cell therapy in Mumbai - India Today

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Stem cell treatment begins for dystrophy patients from Bangladesh – Daily News & Analysis

By JoanneRUSSELL25

Three Bangladeshis suffering from a highly debilitating muscular dystrophy, who arrived in Mumbai on Sunday have begun their treatment at a Navi Mumbai spine clinic.

Abdus, Rahinul and Shorab aged 24, 14 and 8 respectively were diagnosed with this crippling disease at the time of their birth.

They arrived on Sunday evening and we started the treatment on Monday, said Avantika Patil, spokesperson NeuroGen Brain and Spine Institute in Seawoods, Navi Mumbai, who is treating them for free.

They are undergoing an autologous bone marrow derived stem cell treatment. Stem cells are taken from the bone marrow in their hip bone, treated in our lab and then injected into to the patients again. We will provide a combination of stem cell therapy and neuro-rehabilitation which will also includes yoga and speech therapy sessions, Patil explained.

While the hospital is not willing to say what kind of progress can be expected in these particular cases, they revealed that in one case, a bed-ridden patient was able to walk slowly after six years of treatment.

In January, fruit seller Tofazzal Hossain sparked a rare debate about euthanasia in conservative Bangladesh in January when he pleaded with the authorities to allow his grandson and two sons to die.

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Stem cell treatment begins for dystrophy patients from Bangladesh - Daily News & Analysis

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Stem-cell therapy – Wikipedia

By NEVAGiles23

This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( http://www.clinicaltrials.gov NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

Research currently conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[70][71][72][73] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[74] Companion animals can serve as clinically relevant models that closely mimic human disease.[75][76]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. http://www.researchgate.net/publication/281712114_Treatment_of_Long_Standing_Multiple_Sclerosis_with_Regentime_Stem_Cell_Technique The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

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