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Prognosis of Spinal Cord Injuries |

By Dr. Matthew Watson

The prognosis for spinal cord injuries varies depending on the severity of the injury. There is always hope of recovering some function with spinal cord injuries. The completeness and location of the injury will determine the prognosis.

There are two levels of completeness in spinal cord injuries which impact the outlook:

Spinal cord injuries in which the patient has not experienced paralysis have the greatest chance of recovery. However, those patients who do experience paralysis still have a remarkable chance that is improving with research every day. The sooner treatments are implemented to strengthen muscles below the level of the spinal cord injury, the better the prognosis.

The first year of recovery is the hardest as the patient is just beginning to adjust to his or her condition. The use of physical and occupational therapy during this time is the key to recovery. The extent of the function fully returning is typically seen in the first two years after the initial injury.

Treatment options vary with each spinal cord injury, but typically include:

Mental health is a huge part of recovery for the spinal cord injury patient. Anxiety and depression are common in spinal cord injury patients. These patients will go through good days, and not so good days.

There may be days where the patient wants to give up completely on treatments, and will wonder if it is all worth it. Keeping up with the mental health of the spinal cord injury patient is incredibly important for the overall recovery. Mental health has been proven to directly relate to physical health.

Having a good support system is incredibly important to the overall outlook of a spinal cord injury patient. Spinal cord injury patients will need both physical and emotional support.

Caregivers should continually provide patients with:

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Hematopoietic Stem Cells: What Diseases Can these Stem …

By Dr. Matthew Watson

Hematopoietic stem cells (HSCs) are defined as stem cells that have a preference for becoming cells of the blood and immune system, such as white bloodcells, red bloodcells, and platelets. Found in the peripheral blood and bone marrow,hematopoietic stem cells are also present in plentiful supply within the umbilical cord blood of newborn babies.

For the past thirty years, cord blood has been used within transplant medicine, including for the treatment of leukemia and other blood diseases. For most conditions in which a bone marrow or peripheral blood stem cell transplant is an option, a cord blood transplant is a potential alternative.

In this article:

Hematopoietic stem cells(HSCs) are thestem cellsthat repopulate the blood and immune system within humans, via a process known ashaematopoiesis. For this reason, hematopoietic stem cell transplantation, better known as HSCT, can be a promising treatment approach for a wide range of conditions.

The use of human cord blood cells dates back as early as 1974, when it was first proposed that stem cell and progenitor cells were present in human cord blood.By 1983, the use of cord blood as an alternative to bone marrow had been proposed. Five years later in 1988, the first successful cord blood transplant to restore a patients blood and immune system cells took place in France.

In addition to a long history of use within transplant medicine, human cord blood cells are playing a growing role within regenerative medicine. Cord blood stem cells have been induced to develop into neural cells, suggesting that they may represent a potential treatment for neurological conditions, such as Alzheimers, Parkinsons, spinal cord injury, dementia, and related conditions.

Human cord blood cells can also develop into blood vessels, making them promising for the repair of tissues following stroke, coronary heart disease, rheumatic heart disease, congestive heart failure, and congenital heart conditions.

What Are the Benefits of Banking #CordBlood? The main benefit to banking cord blood is it allows parents to preserve stem cells for future medical use. Many parts of the body do not regenerate, so they are at risk of failing

BioInformant (@StemCellMarket) July 23, 2018

It is also interesting to consider the common disease categories treatable with cord blood transplant, as shown in the table below.

There are more than 80 medical conditions for which transplantation of hematopoietic stem cells (including cord blood transplant) is a standard treatment option. Most of these therapies require allogeneic transplants, where the patient must use a genetically-matched cord blood donor. The only exceptions to this are patients who are transplanted for solid tumors or acquired anemias. In these situations, the patient may receive an autologous transplant.

Comprehensive lists of conditions treatable with hematopoietic stem cells are available here and here.

In addition, there is a range of disease categories for which cord blood transplant could represent a viable treatment method in the future. For these conditions, there are still unknown criteria that need to be determined before the cord blood stem cell transplant can become commonplace, such as patient criteria for optimal treatment effectiveness, optimum stem cell quantity for use in transplant, and preferred method of stem cell delivery into the patient, as shown below.

Download this infographic now and reference it later.

What do you think of the future of hematopoietic stem cell transplant? Share your thoughts in the comments below.

Hematopoietic Stem Cells: What Diseases Can these Stem Cells Treat?

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Neural Stem Cells – Stemcell Technologies

By Dr. Matthew Watson

The Central Nervous System

The mature mammalian central nervous system (CNS) is composed of three major differentiated cell types: neurons, astrocytes and oligodendrocytes. Neurons transmit information through action potentials and neurotransmitters to other neurons, muscle cells or gland cells. Astrocytes and oligodendrocytes, collectively called glial cells, play important roles of their own, in addition to providing a critical support role for optimal neuronal functioning and survival. During mammalian embryogenesis, CNS development begins with the induction of the neuroectoderm, which forms the neural plate and then folds to give rise to the neural tube. Within these neural structures there exists a complex and heterogeneous population of neuroepithelial progenitor cells (NEPs), the earliest neural stem cell type to form.1,2 As CNS development proceeds, NEPs give rise to temporally and spatially distinct neural stem/progenitor populations. During the early stage of neural development, NEPs undergo symmetric divisions to expand neural stem cell (NSC) pools. In the later stage of neural development, NSCs switch to asymmetric division cycles and give rise to lineage-restricted progenitors. Intermediate neuronal progenitor cells are formed first, and these subsequently differentiate to generate to neurons. Following this neurogenic phase, NSCs undergo asymmetric divisions to produce glial-restricted progenitors, which generate astrocytes and oligodendrocytes. The later stage of CNS development involves a period of axonal pruning and neuronal apoptosis, which fine tunes the circuitry of the CNS. A previously long-held dogma maintained that neurogenesis in the adult mammalian CNS was complete, rendering it incapable of mitotic divisions to generate new neurons, and therefore lacking in the ability to repair damaged tissue caused by diseases (e.g. Parkinsons disease, multiple sclerosis) or injuries (e.g. spinal cord and brain ischemic injuries). However, there is now strong evidence that multipotent NSCs do exist, albeit only in specialized microenvironments, in the mature mammalian CNS. This discovery has fuelled a new era of research into understanding the tremendous potential that these cells hold for treatment of CNS diseases and injuries.

Neurobiologists routinely use various terms interchangeably to describe undifferentiated cells of the CNS. The most commonly used terms are stem cell, precursor cell and progenitor cell. The inappropriate use of these terms to identify undifferentiated cells in the CNS has led to confusion and misunderstandings in the field of NSC and neural progenitor cell research. However, these different types of undifferentiated cells in the CNS technically possess different characteristics and fates. For clarity, the terminology used here is:

Neural Stem Cell (NSCs): Multipotent cells which are able to self-renew and proliferate without limit, to produce progeny cells which terminally differentiate into neurons, astrocytes and oligodendrocytes. The non-stem cell progeny of NSCs are referred to as neural progenitor cells.

Neural Progenitor Cell: Neural progenitor cells have the capacity to proliferate and differentiate into more than one cell type. Neural progenitor cells can therefore be unipotent, bipotent or multipotent. A distinguishing feature of a neural progenitor cell is that, unlike a stem cell, it has a limited proliferative ability and does not exhibit self-renewal.

Neural Precursor Cells (NPCs): As used here, this refers to a mixed population of cells consisting of all undifferentiated progeny of neural stem cells, therefore including both neural progenitor cells and neural stem cells. The term neural precursor cells is commonly used to collectively describe the mixed population of NSCs and neural progenitor cells derived from embryonic stem cells and induced pluripotent stem cells.

Prior to 1992, numerous reports demonstrated evidence of neurogenesis and limited in vitro proliferation of neural progenitor cells isolated from embryonic tissue in the presence of growth factors.3-5 While several sub-populations of neural progenitor cells had been identified in the adult CNS, researchers were unable to demonstrate convincingly the characteristic features of a stem cell, namely self-renewal, extended proliferative capacity and retention of multi-lineage potential. In vivo studies supported the notion that proliferation occurred early in life, whereas the adultCNS was mitotically inactive, and unable to generate new cells following injury. Notable exceptions included several studies in the 1960s that clearly identified a region of the adult brain that exhibited proliferation (the forebrain subependyma)6 but this was believed to be species-specific and was not thought to exist in all mammals. In the early 1990s, cells that responded to specific growth factors and exhibited stem cell features in vitro were isolated from the embryonic and adult CNS.7-8 With these studies, Reynolds and Weiss demonstrated that a rare population of cells in the adult CNS exhibited the defining characteristics of a stem cell: self-renewal, capacity to produce a large number of progeny and multilineage potential. The location of stem cells in the adult brain was later identified to be within the striatum,9 and researchers began to show that cells isolated from this region, and the dorsolateral region of the lateral ventricle of the adult brain, were capable of differentiating into both neurons and glia.10

During mammalian CNS development, neural precursor cells arising from the neural tube produce pools of multipotent and more restricted neural progenitor cells, which then proliferate, migrate and further differentiate into neurons and glial cells. During embryogenesis, neural precursor cells are derived from the neuroectoderm and can first be detected during neural plate and neural tube formation. As the embryo develops, neural stem cells can be identified in nearly all regions of the embryonic mouse, rat and human CNS, including the septum, cortex, thalamus, ventral mesencephalon and spinal cord. NSCs isolated from these regions have a distinct spatial identity and differentiation potential. In contrast to the developing nervous system, where NSCs are fairly ubiquitous, cells with neural stem cell characteristics are localized primarily to two key regions of the mature CNS: the subventricular zone (SVZ), lining the lateral ventricles of the forebrain, and the subgranular layer of thedentate gyrus of the hippocampal formation (described later).11 In the adult mouse brain, the SVZ contains a heterogeneous population of proliferating cells. However, it is believed that the type B cells (activated GFAP+/PAX6+ astrocytes or astrogliallike NSCs) are the cells that exhibit stem cell properties, and these cells may be derived directly from radial glial cells, the predominant neural precursor population in the early developing brain. NPCs in this niche are relatively quiescent under normal physiological conditions, but can be induced to proliferate and to repopulate the SVZ following irradiation.10 SVZ NSCs maintain neurogenesis throughout adult life through the production of fast-dividing transit amplifying progenitors (TAPs or C cells), which then differentiate and give rise to neuroblasts. TAPs and neuroblasts migrate through the rostral migratory stream (RMS) and further differentiate into new interneurons in the olfactory bulb. This ongoing neurogenesis, which is supported by the NSCs in the SVZ, is essential for maintenance of the olfactory system, providing a source of new neurons for the olfactory bulb of rodents and the association cortex of non-human primates.12 Although the RMS in the adult human brain has been elusive, a similar migration of neuroblasts through the RMS has also been observed.13 Neurogenesis also persists in the subgranular zone of the hippocampus, a region important for learning and memory, where it leads to the production of new granule cells. Lineage tracing studies have mapped the neural progenitor cells to the dorsal region of the hippocampus, in a collapsed ventricle within the dentate gyrus.10 Studies have demonstrated that neurogenic cells from the subgranular layer may have a more limited proliferative potential than the SVZ NSCs and are more likely to be progenitor cells than true stem cells.14 Recent evidence also suggests that neurogenesis plays a different role in the hippocampus than in the olfactory bulb. Whereas the SVZ NSCs play a maintenance role, it is thought that hippocampal neurogenesis serves to increase the number of new neurons and contributes to hippocampal growth throughout adult life.12 Neural progenitor cells have also been identified in the spinal cord central canal ventricular zone and pial boundary15-16, and it is possible that additional regional progenitor populations will be identified in the future.

In vitro methodologies designed to isolate, expand and functionally characterize NSC populations have revolutionized our understanding of neural stem cell biology, and increased our knowledge of the genetic and epigenetic regulation of NSCs.17 Over the past several decades, a number of culture systems have been developed that attempt to recapitulate the distinct in vivo developmental stages of the nervous system, enabling theisolation and expansion of different NPC populations at different stages of development. Here, we outline the commonly used culture systems for generating NPCs from pluripotent stem cells (PSCs), and for isolating and expanding NSCs from the early embryonic, postnatal and adult CNS.

Neural induction and differentiation of pluripotent stem cells: Early NPCs can be derived from mouse and human PSCs, which include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), using appropriate neural induction conditions at the first stage of differentiation. While these neural differentiation protocols vary widely, a prominent feature in popular embryoid body-based protocols is the generation of neural rosettes, morphologically identifiable structures containing NPCs, which are believed to represent the neural tube. The NPCs present in the neural rosette structures are then isolated, and can be propagated to allow NPC expansion, while maintaining the potential to generate neurons and glial cells. More recently, studies have shown that neural induction of PSCs can also be achieved in a monolayer culture system, wherein human ESCs and iPSCs are plated onto a defined matrix, and exposed to inductive factors.18 A combination of specific cytokines or small molecules, believed to mimic the developmental cues for spatiotemporal patterning in the developing brain during embryogenesis, can be added to cultures at the neural induction stage to promote regionalization of NPCs. These patterned NPCs can then be differentiated into mature cell types with phenotypes representative of different regions of the brain.19-24 New protocols have been developed to generate cerebral organoids from PSC-derived neural progenitor cells. Cerebral organoids recapitulate features of human brain development, including the formation of discrete brain regions featuring characteristic laminar cellular organization.25

Neurosphere culture: The neurosphere culture system has been widely used since its development as a method to identify NSCs.26-29 A specific region of the CNS is microdissected, mechanically or enzymatically dissociated, and plated in adefined serum-free medium in the presence of a mitogenic factor, such as epidermal growth factor (EGF) and/or basic fibroblast growth factor (bFGF). In the neurosphere culture system, NSCs, as well as neural progenitor cells, begin to proliferate in response to these mitogens, forming small clusters of cells after 2 - 3 days. The clusters continue to grow in size, and by day 3 - 5, the majority of clusters detach from the culture surface and begin to grow in suspension. By approximately day seven, depending on the cell source, the cell clusters, called neurospheres, typically measure 100 - 200 m in diameter and are composed of approximately 10,000 - 100,000 cells. At this point, the neurospheres should be passaged to prevent the cell clusters from growing too large, which can lead to necrosis as a result of a lack of oxygen and nutrient exchange at the neurosphere center. To passage the cultures, neurospheres are individually, or as a population, mechanically or enzymatically dissociated into a single cell suspension and replated under the same conditions as the primary culture. NSCs and neural progenitor cells again begin to proliferate to form new cell clusters that are ready to be passaged approximately 5 - 7 days later. By repeating the above procedures for multiple passages, NSCs present in the culture will self-renew and produce a large number of progeny, resulting in a relatively consistent increase in total cell number over time. Neurospheres derived from embryonic mouse CNS tissue treated in this manner can be passaged for up to 10 weeks with no loss in their proliferative ability, resulting in a greater than 100- fold increase in total cell number. NSCs and neural progenitors can be induced to differentiate by removing the mitogens and plating either intact neurospheres or dissociated cells on an adhesive substrate, in the presence of a low serum-containing medium. After several days, virtually all of the NSCs and progeny will differentiate into the three main neural cell types found in the CNS: neurons, astrocytes and oligodendrocytes. While the culture medium, growth factor requirements and culture protocols may vary, the neurosphere culture system has been successfully used to isolate NSCs and progenitors from different regions of the embryonic and adult CNS of many species including mouse, rat and human.

Adherent monolayer culture: Alternatively, cells obtained from CNS tissues can be cultured as adherent cultures in a defined, serum-free medium supplemented with EGF and/or bFGF, in the presence of a substrate such as poly-L-ornithine, laminin, or fibronectin. When plated under these conditions, the neural stem and progenitor cells will attach to the substrate-coated cultureware, as opposed to each other, forming an adherent monolayer of cells, instead of neurospheres. The reported success of expanding NSCs in long-term adherent monolayer cultures is variable and may be due to differences in the substrates, serum-free media andgrowth factors used.17 Recently, protocols that have incorporated laminin as the substrate, along with an appropriate serum-free culture medium containing both EGF and bFGF have been able to support long-term cultures of neural precursors from mouse and human CNS tissues.30-32 These adherent cells proliferate and become confluent over the course of 5 - 10 days. To passage the cultures, cells are detached from the surface by enzymatic treatment and replated under the same conditions as the primary culture. It has been reported that NSCs cultured under adherent monolayer conditions undergo symmetric divisions in long-term culture.30,33 Similar to the neurosphere culture system, adherently cultured cells can be passaged multiple times and induced to differentiate into neurons, astrocytes and oligodendrocytes upon mitogen removal and exposure to a low serum-containing medium.

Several studies have suggested that culturing CNS cells in neurosphere cultures does not efficiently maintain NSCs and produces a heterogeneous cell population, whereas culturing cells under serum-free adherent culture conditions does maintain NSCs.17 While these reports did not directly compare neurosphere and adherent monolayer culture methods using the same medium, growth factors or extracellular matrix to evaluate NSC numbers, proliferation and differentiation potential, they emphasize that culture systems can influence the in vitro functional properties of NSCs and neural progenitors. It is important that in vitro methodologies for NSC research are designed with this caveat in mind, and with a clear understanding of what the methodologies are purported to measure.34-35

Immunomagnetic or immunofluorescent cell isolation strategies using antibodies directed against cell surface markers present on stem cells, progenitors and mature CNS cells have been applied to the study of NSCs. Similar to stem cells in other systems, the phenotype of CNS stem cells has not been completely determined. Expression, or lack of expression, of CD34, CD133 and CD45 antigens has been used as a strategy for the preliminary characterization of potential CNS stem cell subsets. A distinct subset of human fetal CNS cells with the phenotype CD133+ 5E12+ CD34- CD45- CD24-/lo has the ability to form neurospheres in culture, initiate secondary neurosphere formation, and differentiate into neurons and astrocytes.36 Using a similar approach, fluorescence-activated cell sorting (FACS)- based isolation of nestin+ PNA- CD24- cells from the adult mouse periventricular region enabled significant enrichment of NSCs(80% frequency in sorted population, representing a 100-fold increase from the unsorted population).37 However, the purity of the enriched NSC population was found to be lower when this strategy was reevaluated using the more rigorous Neural Colony-Forming Cell (NCFC) assay.38-39 NSC subsets detected at different stages of CNS development have been shown to express markers such as nestin, GFAP, CD15, Sox2, Musashi, CD133, EGFR, Pax6, FABP7 (BLBP) and GLAST40-45. However, none of these markers are uniquely expressed by NSCs; many are also expressed by neural progenitor cells and other nonneural cell types. Studies have demonstrated that stem cells in a variety of tissues, including bone marrow, skeletal muscle and fetal liver can be identified by their ability to efflux fluorescent dyes such as Hoechst 33342. Such a population, called the side population, or SP (based on its profile on a flow cytometer), has also been identified in both mouse primary CNS cells and cultured neurospheres.46 Other non-immunological methods have been used to identify populations of cells from normal and tumorigenic CNS tissues, based on some of the in vitro properties of stem cells, including FABP7 expression and high aldehyde dehydrogenase (ALDH) enzyme activity. ALDH-bright cells from embryonic rat and mouse CNS have been isolated and shown to have the ability to generate neurospheres, neurons, astrocytes and oligodendrocytes in vitro, as well as neurons in vivo, when transplanted into the adult mouse cerebral cortex.47-50 NeuroFluor CDr3 is a membrane-permeable fluorescent probe that binds to FABP7 and can be used to detect and isolate viable neural progenitor cells from multiple species.42-43

Multipotent neural stem-like cells, known as brain tumor stem cells (BTSCs) or cancer stem cells (CSCs), have been identified and isolated from different grades (low and high) and types of brain cancers, including gliomas and medulloblastomas.51-52 Similar to NSCs, these BTSCs exhibit self-renewal, high proliferative capacity and multi-lineage differentiation potential in vitro. They also initiate tumors that phenocopy the parent tumor in immunocompromised mice.53 No unique marker of BTSCs has been identified but recent work suggests that tumors contain a heterogenous population of cells with a subset of cells expressing the putative NSC marker CD133.53 CD133+ cells purified from primary tumor samples formed primary tumors, when injected into primary immunocompromised mice, and secondary tumors upon serial transplantation into secondary recipient mice.53 However, CD133 is also expressed by differentiated cells in different tissues and CD133- BTSCs can also initiate tumors in immunocompromised mice.54-55 Therefore, it remains to bedetermined if CD133 alone, or in combination with other markers, can be used to discriminate between tumor initiating cells and non-tumor initiating cells in different grades and types of brain tumors. Recently, FABP7 has gained traction as a CNS-specific marker of NSCs and BTSCs.42-43, 57

Both the neurosphere and adherent monolayer culture methods have been applied to the study of BTSCs. When culturing normal NSCs, the mitogen(s) EGF (and/or bFGF) are required to maintain NSC proliferation. However, there is some indication that these mitogens are not required when culturing BTSCs.57 Interestingly, the neurosphere assay may be a clinically relevant functional readout for the study of BTSCs, with emerging evidence suggesting that renewable neurosphere formation is a significant predictor of increased risk of patient death and rapid tumor progression in cultured human glioma samples.58-60 Furthermore, the adherent monolayer culture has been shown to enable pure populations of glioma-derived BTSCs to be expanded in vitro.61

Research in the field of NSC biology has made a significant leap forward over the past ~30 years. Contrary to the beliefs of the past century, the adult mammalian brain retains a small number of true NSCs located in specific CNS regions. The identification of CNS-resident NSCs and the discovery that adult somatic cells from mouse and human can be reprogrammed to a pluripotent state,62-68 and then directed to differentiate into neural cell types, has opened the door to new therapeutic avenues aimed at replacing lost or damaged CNS cells. This may include transplantation of neural progenitors derived from fetal or adult CNS tissue, or pluripotent stem cells. Recent research has shown that adult somatic cells can be directly reprogrammed to specific cell fates, such as neurons, using appropriate transcriptional factors, bypassing the need for an induced pluripotent stem cell intermediate.69 Astroglia from the early postnatal cerebracortex can be reprogrammed in vitro to neurons capable of action potential firing, by the forced expression of a single transcription factor, such as Pax6 or the pro-neural transcription factor neurogenin-2 (Neurog2).70 To develop cell therapies to treat CNS injuries and diseases, a greater understanding of the cellular and molecular properties of neural stem and progenitor cells is required. To facilitate this important research, STEMCELL Technologies has developed NeuroCult proliferation and differentiation kits for human, mouse and rat, including xenofree NeuroCult-XF. The NeuroCult NCFC Assay provides a simple and more accurate assay to enumerate NSCs compared to the neurosphere assay. These tools for NSC research are complemented by the NeuroCult SM Neuronal Culture Kits, specialized serum-free medium formulations for culturing primary neurons. Together, these reagents help to advance neuroscience research and assist in its transition from the experimental to the therapeutic phase.

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Pricing Of Approved Cell Therapy Products – BioInformant

By Dr. Matthew Watson

Swiss pharmaceutical giant Novartis made history as the first company to win FDA approval for a CAR-T therapy in the United States. Novartis announced that its genetically modified autologous (self-derived) immunocellular therapy, Kymriah, will cost $475,000 per treatment course. Shortly thereafter, Kite Pharma announced the approval of its CAR-T therapy, Yescarta, in the U.S. with a list price of $373,000. While these prices are expensive, they are far from trendsetting.

In this article:

Pricing of cell therapies is controversialbecause most cell therapy products are priced exponentially higher than traditional drugs. Unfortunately, most drugs can be manufactured and stockpiled in large quantities for off-the-shelf use, while cell therapies involve living cells that require a different approach to commercial-scale manufacturing, transit, stockpiling, and patient use.

To date, the highest priced treatment has not been a cell therapy, but a gene therapy (Glybera). At the time of its launch, Glybera was the first gene therapy approved in the Western world, launching for sale in Germany at a cost close to $1 million per treatment.[1] The record-breaking price tag got revealed in November 2014, when Uniqure and its marketing partner Chiesi, filed a pricing dossier with German authorities to launch Glybera. Unfortunately, Glybera was later withdrawn from the European market due to lack of sales.

Following the approval of Glybera, Kymriah, Yescarta, and more than a dozen other cell therapies, conversations surrounding pricing and reimbursement have become a focal point within the cell therapy industry.

In contrast to pharmaceutical drugs, cell therapies require a different pricing analysis. Below, price tags are shown for approved cell therapy products that have reached the market (prices in US$) and for which there is standardized market pricing.

Pricing of Approved Cell Therapy Products:

Apligrafby Organogenesis & Novartis AG in USA = $1,500-2,500 per use [2]Carticelby Genzyme in USA = $15,000 to $35,000 [3]Cartistemby MEDIPOST in S. Korea = $19,000-21,000 [4],[5]Cupistemby Anterogen in South Korea = $3,000-5,000 per treatment [6]ChondroCelectby Tigenix in EU = ~ $24,000 (20,000) [7]Dermagraftby Advanced Tissue Science in USA = $1,700 per application [8],[9]Epicelby Vericel in theUnited States = $6,000-10,000 per 1% of total body surface area [10]Hearticellgramby FCB-Pharmicell in South Korea = $19,000 [11]HeartSheetby Terumo in Japan = $56,000 (6,360,000) for HeartSheet A Kit; $15,000 (1,680,000) for HeartSheet B Kit (*Each administration uses one A Kit and 5 B Kits)[12]Holoclarby Chiesi Framaceutici in EU = Unknown (very small patient population)Kymriahby Novartis in USA = $425,000 per treatment[13]Osteocelby NuVasive in USA = $600 per cc [14],[15]Prochymalby Osiris Therapeutics and Mesoblast in Canada = ~ $200,000 [16]Provengeby Dendreon and Valeant Pharma in USA = $93,000 [17], [18]SpheroxbyCO.DON AG in EU = $9,500 $12,000 (8,000 10,000) per treatment[19]Strimvelisby GSK in EU = $665,000 (One of worlds most expensive therapies) [20],[21]Temcellby JCR Pharmaceuticals Co. Ltd. in Japan = $115,000-170,000 [22]*Pricing of TEMCELL is $7,600 (868,680 per bag), with one bag of 72m cells administered twice weekly and 2m cells/kg of body weight required per administration[23]Yescartaby Kite Pharma in USA =$373,000[24]

As shown in the list above, wound care products tend to have the lowest cell therapy pricing, typically costing $1,500 to $2,500 per use. For example, Apligrafis created from cells found in healthy human skin and is used to heal ulcers that do not heal after 3-4 weeks ($1,500-2,500 per use), and Dermagraftis a skin substitute that is placed on your ulcer to cover it and to help it heal ($1,700 per application).

Interestingly, Epicel is a treatment for deep dermal or full thickness burns comprising a total body surface area of greater than or equal to 30%. It has higher pricing of $6,000-10,000 per 1% of total body surface area, because it is not used to treat a single wound site, but rather used to treat a large surface area of the patients body.

Next, cartilage-based cell therapy products tend to have mid-range pricing of $10,000 to $35,000. For example, Carticelis a product that consists of autologous cartilage cells (pricing of $15,000 to $35,000), CARTISTEM is a regenerative treatment for knee cartilage (pricing of $19,000 to $21,000), and ChondroCelectis a suspension for implantation that contains cartilage cells (pricing of $24,000).In July 2017,the EMA in Europe also approved Spheroxas a product for articular cartilage defects of the knee with a pricing of$9,500 $12,000 (8,000 10,000) per treatment.

The next most expensive cell therapy products are the ones that are administered intravenously, which range in price from approximately $90,000 to $200,000. For example, Prochymal is an intravenously administered allogenic MSC therapy derived from the bone marrow of adult donors (pricing of $200,000), Provenge is an intravenously administered cancer immunotherapy for prostate cancer ($93,000), and Temcell is an intravenously administered autologous MSC product for the treatment of acute GVHD after an allogeneic bone marrow transplant (pricing of $115,000-170,000).

Finally, many of the worlds most expensive cell therapies are gene therapies, ranging in price from $500,000 to $1,000,000. For example, Kymriah is the first CAR-T cell therapy to be FDA approved in the United States (pricing of $475,00 per treatment course).Strimvelis isan ex-vivo stem cell gene therapy to treat patients with a very rare disease called ADA-SCID (pricing of $665,000).

Although these generalizations do not hold true for every cell therapy product, they explain the majority of cell therapy pricing and provide a valuable model for estimating cell therapy pricing and reimbursement. This information is summarized in the following table.

TABLE. Pricing Scale for Approved Cell Therapies

Another point of reference is also valuable. The RIKEN Institute launched the worlds first clinical trial involving an iPSC-derived product when it transplanted autologous iPSC-derived RPE cells into a human patient in 2014.While the trial was later suspended due to safety concerns, it resumed in 2016, this time using an allogeneic iPSC-derived cell product.

The research team indicated that by using stockpiled iPS cells, the time needed to prepare for a graft can be reduced from 11 months to as little as one month, and the cost, currently around 100 million ($889,100), can be cut to one-fifth or less.[25]

While many factors contribute to cell therapy pricing, key variables that can be used to predict market pricing include:

Another compounding factor is market size, because wound healing and cartilage replacement therapies have significant patient populations, while several of the more expensive therapies address smaller patient populations.[26]

To learn more about this rapidly expanding industry, view the Global Regenerative Medicine Industry Database Featuring 700+ Companies Worldwide.

What variable do you think influence the cost of cell therapies? Share your thoughts in the comments below.

BioInformant is the first and only market research firm to specialize in the stem cell industry. Our research has been cited by major news outlets that include the Wall Street Journal, Nature Biotechnology, Xconomy, and Vogue Magazine. Serving industry leaders that include GE Healthcare, Pfizer, Goldman Sachs, and Becton Dickinson. BioInformant is your global leader in stem cell industry data.

Footnotes[1] $1-Million Price Tag For Glybera Gene Therapy: Trade Secrets. Available at Web. 21 Aug. 2017.[2] 2017 Apligraf Medicare Product and Related Procedure Payment, Organogenesis. Available at: Web. 3 Mar. 2017.[3] CARTICEL (Autologous Chondrocyte Implantation, Or ACI). Available at: Web. 3 Aug. 2017.[4] Cartistem?, What. What Is The Cost Of Cartistem? Available at: N.p., 2017. Web. 3 Mar. 2017.[5] Cartistem. Available at: Web. 3 Aug. 2017.[6] Stem Art, Stem Cell Therapy Pricing. Available at: Web. 3 Mar. 2017.[7]Are Biosimilar Cell Therapy Products Possible? Presentation by Christopher A Bravery [PDF]. Available at: Web. 3 Aug. 2017.[8] Artificial Skin, Presentation by Nouaying Kue (BME 281). Available at: Web. 3 Mar. 2017.[9] Allenet, et al. Cost-effectiveness modeling of Dermagraft for the treatment of diabetic foot ulcers in the french context. Diabetic Metab. 2000 Apr;26(2):125-32.[10] Epicel Skin Grafts, Sarah Schlatter, Biomedical Engineering, University of Rhode Island. Available at: Web. 31 July. 2017.[11] Nature. (2011). South Koreas stem cell approval. [online] Available at: Web. 3 Sept. 2017.[12] Novick, Coline Lee. Translated version of the first two pages of Terumos Conditionally Approved HeartSheet NHI Reimbursement Price. [Twitter Post] Available Web. 21 Sep. 2017.[13] (2017). Is $475,000 Too High a Price for Novartiss Historic Cancer Gene Therapy? [online] Available at: Web. 8 Sept. 2017.[14] Skovrlj, Branko et al. Cellular Bone Matrices: Viable Stem Cell-Containing Bone Graft Substitutes. The Spine Journal 14.11 (2014): 2763-2772. Available at: Web. April 12, 2017.[15] Hiltzik, Michael. Sky-High Price Of New Stem Cell Therapies Is A Growing Concern. Available at: Web. 1 Sept. 2017.[16] Counting Coup: Is Osiris Losing Faith In Prochymal?, Busa Consulting LLC. Available at: Web. 3 Aug. 2017.[17] Dendreon Sets Provenge Price At $93,000, Says Only 2,000 People Will Get It In First Year | Xconomy. Available at: Web. 3 Mar. 2017.[18] Dendreon: Provenge To Cost $93K For Full Course Of Treatment | Fiercebiotech. Available at: Web. 3 Mar. 2017.[19]Warberg Research.CO.DON (CDAX, Health Care). Available at: Web. 21 Sept. 2017.[20] GSK Inks Money-Back Guarantee On $665K Strimvelis, Blazing A Trail For Gene-Therapy Pricing | Fiercepharma. Available at: Web. 3 Mar. 2017.[21] Strimvelis. Available at: Web. 13 Aug. 2017.[22] MesoblastS Japan Licensee Receives Pricing For TEMCELL HS Inj. For Treatment Of Acute Graft Versus Host Disease. Mesoblast Limited, GlobeNewswire News Room. Available at: Web. 3 Mar. 2017.[23]TEMCELL HS Inj. Receives NHI Reimbursement Price Listing, JCR Pharmaceuticals Co., Ltd. News Release, November 26, 2015. Available at: Web. 3 Mar. 2017.[24]Kites Yescarta (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy. Business Wire.Web. 19 Oct. 2017.[25]Riken-Linked Team Set To Test Transplanting Eye Cells Using Ips From Donor | The Japan Times. The Japan Times. N.p., 2017. Web. 23 July. 2017.[26]LinkedIn Comment, by David Caron. Available at: Web. 21 Sept. 2017.

Pricing Of Approved Cell Therapy Products Stem Cells, CAR-T, And More

Pricing Of Approved Cell Therapy Products - BioInformant

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Gene & Cell Therapy FAQs | ASGCT – American Society of …

By Dr. Matthew Watson

The challenges of gene and cell therapists can be divided into three broad categories based on disease, development of therapy, and funding.

Challenges based on the disease characteristics: Disease symptoms of most genetic diseases, such as Fabrys, hemophilia, cystic fibrosis, muscular dystrophy, Huntingtons, and lysosomal storage diseases are caused by distinct mutations in single genes. Other diseases with a hereditary predisposition, such as Parkinsons disease, Alzheimers disease, cancer, and dystonia may be caused by variations/mutations in several different genes combined with environmental causes. Note that there are many susceptible genes and additional mutations yet to be discovered. Gene replacement therapy for single gene defects is the most conceptually straightforward. However, even then the gene therapy agent may not equally reduce symptoms in patients with the same disease caused by different mutations, and even the samemutationcan be associated with different degrees of disease severity. Gene therapists often screen their patients to determine the type of mutation causing the disease before enrollment into a clinical trial.

The mutated gene may cause symptoms in more than one cell type. Cystic fibrosis, for example, affects lung cells and the digestive tract, so the gene therapy agent may need to replace the defective gene or compensate for its consequences in more than one tissue for maximum benefit. Alternatively, cell therapy can utilizestem cellswith the potential to mature into the multiple cell types to replace defective cells in different tissues.

In diseases like muscular dystrophy, for example, the high number of cells in muscles throughout the body that need to be corrected in order to substantially improve the symptoms makes delivery of genes and cells a challenging problem.

Some diseases, like cancer, are caused by mutations in multiple genes. Although different types of cancers have some common mutations, every tumor from a single type of cancer does not contain the same mutations. This phenomenon complicates the choice of a single gene therapy tactic and has led to the use of combination therapies and cell elimination strategies. For more information on gene and cell therapy strategies to treat cancer, please refer to the Cancer and Immunotherapy summary in the Disease Treatment section.

Disease models in animals do not completely mimic the human diseases and viralvectorsmay infect various species differently. The testing of vectors in animal models often resemble the responses obtained in humans, but the larger size of humans in comparison to rodents presents additional challenges in the efficiency of delivery and penetration of tissue.Gene therapy, cell therapy, and oligonucleotide-based therapy agents are often tested in larger animal models, including rabbit, dog, pig and nonhuman primate models. Testing human cell therapy in animal models is complicated by immune rejections. Furthermore, humans are a very heterogeneous population. Their immune responses to the vectors, altered cells, or cell therapy products may differ or be similar to results obtained in animal models.

Challenges in the development of gene and cell therapy agents: Scientific challenges include the development of gene therapy agents that express the gene in the relevant tissue at the appropriate level for the desired duration of time. There are a lot of issues in that once sentence, and while these issues are easy to state, each one requires extensive research to identify the best means of delivery, how to control sufficient levels or numbers of cells, and factors that influence duration of gene expression or cell survival. After the delivery modalities are determined, identification and engineering of a promoter and control elements (on/off switch and dimmer switch) that will produce the appropriate amount of protein in the target cell can be combined with the relevant gene. This gene cassette is engineered into a vector or introduced into thegenomeof a cell and the properties of the delivery vehicle are tested in different types of cells in tissue culture. Sometimes things go as planned and then studies can be moved onto examination in animal models. In most cases, the gene/cell therapy agent may need to be improved further by adding new control elements to obtain the desired responses in cells and animal models.

Furthermore, the response of the immune system needs to be considered based on the type of gene or cell therapy being undertaken. For example, in gene or cell therapy for cancer, one aim is to selectively boost the existing immune response to cancer cells. In contrast, to treat genetic diseases like hemophilia and cystic fibrosis the goal is for the therapeutic protein to be accepted as an addition to the patients immune system.

If the new gene is inserted into the patients cellularDNA, the intrinsic sequences surrounding the new gene can affect its expression and vice versa. Scientists are now examining short DNA segments that may insulate the new gene from surrounding control elements. Theoretically, these insulator sequences would also reduce the effect of vector control signals in the gene cassette on adjacent cellular genes. Studies are also focusing on means to target insertion of the new gene into safe areas of the genome, to avoid influence on surrounding genes and to reduce the risk of insertional mutagenesis.

Challenges of cell therapy include the harvesting of the appropriate cell populations and expansion or isolation of sufficient cells for one or multiple patients. Cell harvesting may require specific media to maintain the stem cells ability toself-renew and mature into the appropriate cells. Ideally extra cells are taken from the individual receiving therapy. Those additional cells can expand in culture and can be induced to becomepluripotent stem cells(iPS), thus allowing them to assume a wide variety of cell types and avoiding immune rejection by the patient. The long term benefit of stem cell administration requires that the cells be introduced into the correct target tissue and become established functioning cells within the tissue. Several approaches are being investigated to increase the number of stem cells that become established in the relevant tissue.

Another challenge is developing methods that allow manipulation of the stem cells outside the body while maintaining the ability of those cells to produce more cells that mature into the desired specialized cell type. They need to provide the correct number of specialized cells and maintain their normal control of growth and cell division, otherwise there is the risk that these new cells may grow into tumors.

Challenges in funding: In most fields, funding for basic or applied research for gene and cell therapy is available through the National Institutes of Health (NIH) and private foundations. These are usually sufficient to cover the preclinical studies that suggest a potential benefit from a particular gene and cell therapy. Moving into clinical trials remains a huge challenge as it requires additional funding for manufacturing of clinical grade reagents, formal toxicology studies in animals, preparation of extensive regulatory documents, and costs of clinical trials.Biotechnology companies and the NIH are trying to meet the demand for this large expenditure, but many promising therapies are slowed down by lack of funding for this critical next phase.

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Cell Therapy World Asia – IMAPAC – Imagine your Impact

By Dr. Matthew Watson

Globally, the stem cell therapy market is expected to be worth $40 billion by 2020 and $180 billion by 2030. The largest number of marketed cell therapy products is used for the treatment of notably non-healing wounds/skin (46%) and muscular-skeletal injuries (35%). This trend will change as more and stem cell therapy products for cancer and heart disease complete their clinical trials and are approved for market release.

Adult stem cell leads the market due to low contamination during sub-culture and expansion, relatively low labour production and compatibility with the human body.Just the Induced pluripotent stem cells (IPScs) are expected to report revenue of over USD 4.5 billion by 2020, on account of the analogous nature of its origin.With the continued growth of medical tourism hubs like India, Singapore, and Thailand, Asia is expected to maintain its place as the epicentre of stem cell research and therapy. These opportunities include contract research outsourcing and rising patient population with neurological and other chronic conditions in the region. Japan, Singapore and South Korea are the frontrunners and are set to dominate the APAC stem cell market in the coming years.

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Benefits of Plant Stem Cells for Skin & Hair Teadora

By Dr. Matthew Watson

We are thrilled to share an excerpt form Dr. Q Schulte aufm Erley's article on Plant Stem Cells. Dr. Q is an entrepreneur, scientist and founder of one of our most loved partners: Shtrands. Shtrands is a beauty industry innovator. They provide a hair care concierge service that brings you curated products and expert advice to match your hair texture, scalp condition and styling needs.

The highly competitive cosmetics industry is always looking for the next best ingredient(s) that can fight the aging process and this led to a sizable increase in the number of anti-aging products on the market. With this is coming an increased number of active ingredients developed for this category; one of these ingredients is stem cell extract.This is an ingredient that must be assessed carefully, as marketing claims often push the limits of the available science.

The concept of stem cells originated at the end of the 19th century as a theoretical postulate to account for the ability of certain tissues (blood, skin, etc.) to renew themselves for the lifetime of organisms even though they are comprised of short-lived cells. Stem cells isolation and identification happened many years later though.

Stem cells have received a fair share of attention in the public debate mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being.

A stem cell is a generic cell that can make exact copies of itself (daughters) indefinitely. These daughters can remain stem cells or further undergo differentiation (2). Such that a stem cell has the ability to make specialized cells for various tissues in the body, such as heart muscle, skin tissue, and liver tissue.

Because of their self-renewal functions, stem cells are the most important cells in the skin, as they are the source for continuous regeneration of the epidermis. Stem cell cosmetics are developed based on stem cell technology, which involves using extracts or culture media of stem cells. However, cosmetics containing human stem cells or their extracts have not been released into the market due to legal, ethical, and safety concerns. Meanwhile, plant stem cells, which circumvent these problems, are highly regarded in the cosmetics industry for improving culture technology.

The EUprohibits the use of cells, tissues, or products of human origin in cosmetics; stem cell therapy for anti-aging has not been approved or been deemed safe or effective in USA by the FDA. Furthermore, its use outside of a clinical research trial (which would be listed at is prohibited. Whereas the Korea Food and Drug Association has allowed the use of sources originating from stem cell media in cosmetics since 2009 (3).

So, any cosmetics marketed as containing stem cells found on US market (should) contain stem cells extracted from plants.

A major difference between animal and plant stem cells is that plant stem cells provide cells for complete organs (branches, leaves, etc.), compared with the animal stem cells, which regenerate cells restricted to one tissue type.

Plants have nowhere to run when times get tough, so they must rely on an inner body plan to generate developmental responses to environmental changes.

Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation.

There is some confusion around the term stem cell due to the marketing verbiage used by the cosmetic companies. In topical cosmetics the formulations dont contain stem cells straight out of the plants. They are actually a range ofplant stem cell extracts, which are manufactured using a cell culture technology.This technology consists of many and complicated methods that should ensure growth of plant cells, tissues or organs in the environment with a microbe-free nutrient. The plant cell technologyallows synthesis of the biologically active substances that exist in plants, but are not commonly available in natural environment or are difficult to obtain by chemical synthesis.

The extracts obtained through this technology from the plant stem cells are currently used for production of both common or professional care cosmetics (4).

The beneficial apple properties are known for centuries. Apples are cultivated today only for their taste, but earlier the main criterion of the type selection was the shelf life of the fruits.

One of such apple-tree types isUttwiler Spatlauberwhich is growing in Switzerland. This is a type cultivated solely due to a possible long-time storage of fruits, which remain fresh even for several months.Some trees come from the plant cutting sets planted during the 18th century!!!

The stem cell extracts are made in 2 main steps: first, the tissue material is obtained from apples (collected from a cut surfaces of the apples). Secondly, the material is going through a complicated biotechnological process to make the stem cell extracts that contains certain active ingredients. These are actually the ingredients used in formulations marketed as containing stem cells (5).

Swiss biotech company Mibelle Biochemistry created the product named PhytoCellTecTMMalus Domestica, that is a liposomal formulation (extract) derived from the stem cells of the Uttwiler Spatlauber apples. The company has published in vitro experiments done with hair follicles that showed the ability of theUttwiler Spatlauberstem cell extract to delaying of the tissue atrophy process (6); this ingredient delays hair aging.

At Teadora, we chose to includeMibelle'sPhytoCellTecTM Argan Plant Stem Cells in our ButterandBrazilian Glow Oiland here are the details from Mibelle that helped to convince us this ingredient was a must have companion to the huge list of active superfruits we crafted into our products, read on, it's pretty cool:

Deep-Seated Rejuvenation of the Skin:In order to maintain the skin in a healthy condition,cutaneous tissue is being continuously regenerated.This regenerative capacity relies on adult stem cells inthe skin. While considerable research has been done onepidermal stem cells, dermal stem cells were identifiedonly in 2009. The dermis is the middle layer of the skinand gives it tensile strength and elasticity, therefore it isalso the site where wrinkles originate.

PhytoCellTec Argan was developed to improvethe regenerative capacity of dermal stem cells therebyachieving deep-seated rejuvenation of the skin.

PhytoCellTec Argan is a powder based on stem cellsof the argan tree, one of the oldest tree species in theworld.In order to evaluate which active ingredient effectivelypromotes dermal stem cell activity, a stable humandermal papilla cell line was used as a new test system:stem cell activity is assessed based on the expression ofthe Sox2 gene, which is an established stem cell marker.Furthermore, the characteristic property of stem cells togrow in three-dimensional spherical colonies serves asa second observable indicator of stem cell viability inthis assay.

Clinical studies performed on healthy volunteers showedthat PhytoCellTec Argan:

effectively stimulates the regeneration of dermalconnective tissue, thereby increasing skin density

helps the skin to regain its firmness

significantly reduces wrinkle depth in crows feet area.

PhytoCellTec Argan is the very first active ingredientthat is capable of both protecting and vitalizing humandermal stem cells. This will not only help to acceleratethe skins natural repair process but also fights skin agingright at the root. Here are some of the amazing benefits:

Vitalizes and protects dermal stem cells Reduces wrinkles Tightens and tones skin tissues Increases skin firmness and density Deep-seated rejuvenation of the skinFirst cosmetic active with proven results forprotecting and vitalizing dermal stem cells

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Benefits of Plant Stem Cells for Skin & Hair Teadora

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Stem Cell Therapy May Be The Cure For Spinal Cord Injury …

By Dr. Matthew Watson


A stem cell treatment which is in primary stages of trials, has proved effective in treatment when using non-donor stem cells.

Spinal cord injuries can happen to anyone, the condition tends to be a result of a fall or accident, although it can also be an outcome of a brain injury. When the spinal cord is injured the pathway is practically closed. Nerve impulses cant get through, this has problematic symptoms such as; a person suffering paralysis, a loss of mobility and sensation.

Using stem cell therapy where the stem cells havent been donated mean they are more likely to be accepted by the patient when they are injected.

This new trial was published on the 9th of May 2018 inScience Translational Medicine, a team of international scientist led by the University of California San Diego School of Medicine successfully grafted stem cells back into a spinal cord without aggravating the immune system or reducing it in any way.

The stem cells injected in the trial were accepted and survived long term without causing a tumor. Researchers also found that the same cells showed a long-term survival when injected into an injured spinal cord.

Senior author Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine and a member of the Sanford Consortium for Regenerative Medicine, said: The promise of iPSCs is huge, but so too have been the challenges. In this study, weve demonstrated an alternate approach,

We took skin cells, then induced them to becomeneural precursor cells(NPCs), destined to become nerve cells. Because they are syngeneicgenetically identical with the cell-graftthey are immunologically compatible. They grow and differentiate with no immunosuppression required.

Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, said: Using RNA sequencing and innovative bioinformatic method to deconvolute the RNAs species-of-origin, the research team demonstrated that iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue.

In their study, researchers found that the stem cells survived and differentiated into neurons and supporting glial cells. The grafted stem cells were detected to be working and responsive seven months after transplantation.

Researchers, then grafted stem cells into similar tissues in the body that had severespinal cord injuries, this injection of stem cells was then followed by a transient four-week course of drugs that suppress the immune system. The stem cells then could work in the spinal cord and begin to allow movement.

Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting, said Marsala.

Because long-term post-grafting periodsone to two yearsare required to achieve a full graftedcells-induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs.

In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.

The treatment is expected to go to the next stage of trials in the next few years, with the hope that this stem cell therapy can be used in modern medicine.

This research forms another significant step towards stem cell therapy and spinal cord injury. Yet the type of cell used is still in contention when it comes to human application. iPSC are undoubtedlyauseful research tool in the laboratory and as a result because of their pluripotency, many scientists continue to hopethat they can one day be used for therapeutic applications, including regenerative medicine in humans. This strategy continues to proveproblematic ashave been shown to produce lesions and tumors when injected or transplanted.

This type of research does however contribute to ongoing developments for the use of stem cells, where possible use of Adult Stem Cells, known not to be problematic as a result of tumors could be used.

We believe the best stem cells to use in emergingtreatmentswill be the patients own stem cells as this doesnt require a search for a suitable donor and in turn, eliminates chances of the transplanted cells being rejected.

If you want more information on how you can protect your childs future health by banking their cells, get in touch with our friendly team today or order your free information pack.

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Endothelial and cardiac progenitor cells for …

By Dr. Matthew Watson

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Stem cells have the potential to differentiate into cardiovascular cell lineages and to stimulate tissue regeneration in a paracrine/autocrine manner; thus, they have been extensively studied as candidate cell sources for cardiovascular regeneration. Several preclinical and clinical studies addressing the therapeutic potential of endothelial progenitor cells (EPCs) and cardiac progenitor cells (CPCs) in cardiovascular diseases have been performed. For instance, autologous EPC transplantation and EPC mobilization through pharmacological agents contributed to vascular repair and neovascularization in different animal models of limb ischemia and myocardial infarction. Also, CPC administration and in situ stimulation of resident CPCs have been shown to improve myocardial survival and function in experimental models of ischemic heart disease. However, clinical studies using EPC- and CPC-based therapeutic approaches have produced mixed results. In this regard, intracoronary, intra-myocardial or intramuscular injection of either bone marrow-derived or peripheral blood progenitor cells has improved pathological features of tissue ischemia in humans, despite modest or no clinical benefit has been observed in most cases. Also, the intriguing scientific background surrounding the potential clinical applications of EPC capture stenting is still waiting for a confirmatory proof. Moreover, clinical findings on the efficacy of CPC-based cell therapy in heart diseases are still very preliminary and based on small-size studies.

Despite promising evidence, widespread clinical application of both EPCs and CPCs remains delayed due to several unresolved issues. The present review provides a summary of the different applications of EPCs and CPCs for cardiovascular cell therapy and underlies their advantages and limitations.

bone marrow-derived cells

cardiac progenitor cells

C-X-C chemokine receptor type 4

1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine-acetylated low density lipoprotein

endothelial colony forming cells

endothelial progenitor cells

granulocyte colony-stimulating factor

individual patient data

induced pluripotent stem cells

platelet-derived growth factor receptor

stromal cell derived factor-1

stage specific embryonic antigen-1

ST-segment elevation myocardial infarction

vascular endothelial growth factor

Ulex europaeus agglutinin-1

Endothelial progenitor cells

Stem cells



Myocardial infarction

Regenerative medicine

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iPS Cells for Disease Modeling and Drug Discovery

By Dr. Matthew Watson

Cambridge Healthtech Institutes 4th AnnualJune 19-20, 2019

With advances in reprogramming and differentiation technologies, as well as with the recent availability of gene editing approaches, we are finally able to create more complex and phenotypically accurate cellular models based on pluripotent cell technology. This opens new and exciting opportunities for pluripotent stem cell utilization in early discovery, preclinical and translational research. CNS diseases and disorders are currently the main therapeutic area of application with some impressive success stories resulted in clinical trials. Cambridge Healthtech Institutes 4th Annual iPS Cells for Disease Modeling and Drug Discovery conference is designed to bring together experts and bench scientists working with pluripotent cells and end users of their services, researchers working on finding cures for specific diseases and disorders.

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Wednesday, June 19

12:00 pm Registration Open

12:00 Bridging Luncheon Presentation:Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Pre-clinical Safety, Efficacy, and Discovery

Nicholas Geissse, PhD, CSO, NanoSurface Biomedical

Alec S.T. Smith, PhD, Acting Instructor, Bioengineering, University of Washington

hiPSC-CM maturation is sensitive to structural cues from the extracellular matrix (ECM). Failure to reproduce these signals in vitro can hamper experimental reproducibility and fidelity. Engineering approaches that address this gap typically trade off complexity with throughput, making them difficult to deploy in the modern drug development paradigm. The NanoSurface Car(ina) platform leverages ECM engineering approaches that are fully compatible with industry-standard instrumentation including HCI- and MEA-based assays, thereby improving their predictive power.

12:30 Transition to Plenary


2:20Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing

2:25 Meet the Plenary Keynotes

3:05 Chairpersons Remarks

Gabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

3:10 KEYNOTE PRESENTATION: iPSC-Based Drug Discovery Platform for Targeting Innate Immune Cell Responses

Christoph Patsch, PhD, Team Lead Stem Cell Assays, Disease Relevant Cell Models and Assays, Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development

The role of innate immune cells in health and disease, respectively their function in maintaining immune homeostasis and triggering inflammation makes them a prime target for therapeutic approaches. In order to explore novel therapeutic strategies to enhance immunoregulatory functions, we developed an iPSC-based cellular drug discovery platform. Here we will highlight the unique opportunities provided by an iPSC-based drug discovery platform for targeting innate immune cells.

3:40 Phenotypic Screening of Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Discovery and Toxicity Screening

Arne Bruyneel, PhD, Postdoctoral Fellow, Mark Mercola Lab, Cardiovascular Institute, Stanford University School of Medicine

Cardiac arrhythmia and myopathy is a major problem with cancer therapeutics, including newer small molecule kinase inhibitors, and frequently causes heart failure, morbidity and death. However, currentin vitromodels are unable to predict cardiotoxicity, or are not scalable to aid drug development. However, with recent progress in human stem cell biology, cardiac differentiation protocols, and high throughput screening, new tools are available to overcome this barrier to progress.

4:10 Disease Modeling Using Human iPSC-Derived Telencephalic Inhibitory Interneurons - A Couple of Case Studies

Yishan Sun, PhD, Investigator, Novartis Institutes for BioMedical Research (NIBR)

Human iPSC-derived neurons provide the foundation for phenotypic assays assessing genetic or pharmacological effects in a human neurobiological context. The onus is on assay developers to generate application-relevant neuronal cell types from iPSCs, which is not always straightforward, given the diversity of neuronal classes in the human brain and their developmental trajectories. Here we present two case studies to illustrate the use of iPSC-derived telencephalic GABAergic interneurons in neuropsychiatric research.

4:40 Rethinking the Translational The Use of Highly Predictive hiPSC-Derived Models in Pre-Clinical Drug Development

Stefan Braam, CEO, Ncardia

Current drug development strategies are failing to increase the number of drugs reaching the market. One reason for low success rates is the lack of predictive models. Join our talk to learn how to implement a predictive and translational in vitro disease model, and assays for efficacy screening at any throughput.

5:10 4th of July Celebration in the Exhibit Hall with Poster Viewing

5:30 - 5:45 Speed Networking: Oncology

6:05 Close of Day

5:45 Dinner Short Course Registration

6:15 Dinner Short Course*

*Separate registration required.

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Thursday, June 20

7:15 am Registration

7:15 Breakout Discussion Groups with Continental Breakfast

8:10 Chairpersons Remarks

Jeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

8:15 Levering iPSC to Understand Mechanism of Toxicity

Jeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

The discovery of mammalian cardiac progenitor cells suggests that the heart consists of not only terminally differentiated beating cardiomyocytes, but also a population of self-renewing stem cells. We recently showed that iPSC cardiomyocytes can be utilized not only to de-risk compounds with potential for adverse cardiac events, but also to understand underlying mechanisms of cell-specific toxicities following xenobiotic stress, thus preventing differentiation and self-renewal of damaged cells.

8:45Pluripotent Stem Cell-Derived Cardiac and Vascular Progenitor Cells for Tissue Regeneration

Nutan Prasain, PhD, Associate Director, Cardiovascular Programs, Astellas Institute for Regenerative Medicine (AIRM)

This presentation will provide the review on recent discoveries in the derivation and characterization of cardiac and vascular progenitor cells from pluripotent stem cells, and discuss the therapeutic potential of these cells in cardiac and vascular tissue repair and regeneration.

9:15 Use of iPSCDerived Hepatocytes to Identify Treatments for Liver Disease

Stephen A. Duncan, PhD, Smartstate Chair in Regenerative Medicine, Professor and Chairman, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina

MTDPS3 is a rare disease caused by mutations in the DGUOK gene, which is needed for mitochondrial DNA (mtDNA) replication and repair. Patients commonly die as children from liver failure primarily caused by unmet energy requirements. We modeled the disease using DGOUK deficient iPSC derived hepatocytes and performed a screen to identify drugs that can restore mitochondrial ATP production.

9:45Industrial-Scale Generation of Human iPSC-Derived Hepatocytes for Liver-Disease and Drug Development Studies

Liz Quinn, PhD, Associate Director, Stem Cell Marketing, Marketing, Takara Bio USA

Our optimized hepatocyte differentiation protocol and standardized workflow mimics embryonic development and allows for highly efficient differentiation of hPSCs through definitive endoderm into hepatocytes. We will describe the creation of large panels of industrial-scale hPSC-derived hepatocytes with specific genotypes and phenotypes and their utility for drug metabolism and disease modeling.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Poster Winner Announced

11:00 KEYNOTE PRESENTATION: Modeling Human Disease Using Pluripotent Stem Cells

Lorenz Studer, MD, Director, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center

One of the most intriguing applications of human pluripotent stem cells is the possibility of recreating a disease in a dish and to use such cell-based models for drug discovery. Our lab uses human iPS and ES cells for modeling both neurodevelopmental and neurodegenerative disorders. I will present new data on our efforts of modeling complex genetic disease using pluripotent stem cells and the development of multiplex culture systems.

11:30 Preclinical Challenges for Gene Therapy Approaches in Neuroscience

Gabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

Gene therapy has delivered encouraging results in the clinic, and with the first FDA approval for an AAV product is now becoming a reality. This presentation will provide an overview of the most recent advances of gene therapy for the treatment of neurological diseases. The discussion will focus on preclinical considerations for gene therapy including delivery, efficacy, biodistribution, animal models and safety.

12:00 pm Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

Thomas Durcan, PhD, Assistant Professor, Neurology and Neurosurgery, McGill University

Advances in stem cell technology have provided researchers with tools to generate human neurons and develop first-of-their-kind disease-relevant assays. However, it is imperative that we accelerate discoveries from the bench to the clinic and the Montreal Neurological Institute (MNI) and its partners are piloting an Open Science model. By removing the obstacles in distributing patient samples and assay results, our goal is to accelerate translational medical research.

12:30 Elevating Drug Discovery with Advanced Physiologically Relevant Human iPSC-Based Screening Platforms

Fabian Zanella, PhD, Director, Research and Development, StemoniX

Structurally engineered human induced pluripotent stem cell (hiPSC)-based platforms enable greater physiological relevance, elevating performance in toxicity and discovery studies. StemoniXs hiPSC-derived platforms comprise neural (microBrain) or cardiac (microHeart) cells constructed with appropriate inter- and intracellular organization promoting robust activity and expected responses to known cellular modulators.

1:00Overcoming Challenges in CNS Drug Discovery through Developing Translatable iPSC-derived Cell-Based Assays

Jonathan Davila, PhD, CEO, Co-Founder, NeuCyte Inc.

Using direct reprogramming of iPSCs to generate defined human neural tissue, NeuCyte developed cell-based assays with complex neuronal structure and function readouts for versatile pre-clinical applications. Focusing on electrophysiological measurements, we demonstrate the capability of this approach to identify adverse neuroactive effects, evaluate compound efficacy, and serve phenotypic drug discovery.

1:15Enjoy Lunch on Your Own

1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

1:45 - 2:00 Speed Networking: Last Chance to Meet with Potential Partners and Collaborators!

2:20 Chairpersons Remarks

Gary Gintant, PhD, Senior Research Fellow, AbbVie

2:25 The Evolving Roles of Evolving Human Stem Cell-Derived Cardiomyocyte Preparations in Cardiac Safety Evaluations

Gary Gintant, PhD, Senior Research Fellow, AbbVie

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for preclinical cardiac safety testing. Recent applications focus on drug effects on cardiac electrophysiology, contractility, and structural toxicities, with further complexity provided by the growing number of hiPSC-CM preparations being developed that may also promote myocyte maturity. The evolving roles (both non-regulatory and regulatory) of these preparations will be reviewed, along with general considerations for their use in cardiac safety evaluations.

2:55 Pharmacogenomic Prediction of Drug-Induced Cardiotoxicity Using hiPSC-Derived Cardiomyocytes

Paul W. Burridge, PhD, Assistant Professor, Department of Pharmacology, Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine

We have demonstrated that human induced pluripotent stem cell-derived cardiomyocytes successfully recapitulate a patients predisposition to chemotherapy-induced cardiotoxicity, confirming that there is a genomic basis for this phenomenon. Here we will discuss our recent work deciphering the pharmacogenomics behind this relationship, allowing the genomic prediction of which patients are likely to experience this side effect. Our efforts to discover new drugs to prevent doxorubicin-induced cardiotoxicity will also be reviewed.

3:25 Exploring the Utility of iPSC-Derived 3D Cortical Spheroids in the Detection of CNS Toxicity

Qin Wang, PhD, Scientist, Drug Safety Research and Evaluation, Takeda

Drug-induced Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive assays. To address the challenge, we validated a high throughput human iPSC-derived 3D microBrain model with a diverse set of pharmaceuticals. We measured drug-induced changes in neuronal viability and Ca channel function. MicroBrain exposure and analyses were rooted in therapeutic exposure to predict clinical drug-induced seizures and/or neurodegeneration. We found that this high throughput model has very low false positive rate in the prediction of drug-induced neurotoxicity.

3:55 Linking Liver-on-a-Chip and Blood-Brain-Barrier-on-a-Chip for Toxicity Assessment

Sophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine

One of the challenges to reproduce the function of tissues in vitro is the maintenance of differentiation. Essential aspects necessary for such endeavor involve good mechanical and chemical mimicry of the microenvironment. I will present examples of the management of the cellular microenvironment for liver and blood-brain-barrier tissue chips and discuss how on-a-chip devices may be linked for the integrated study of the toxicity of drugs and other molecules.

4:25 Close of Conference

Day 1 | Day 2 | Download Brochure | Speaker Biographies

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

Chemical Biology and Target Validation

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iPS Cells for Disease Modeling and Drug Discovery

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Filling the Gap: Neural Stem Cells as A Promising Therapy …

By Dr. Matthew Watson

Open AccessReview


Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal


ICVS/3BsPT Government Associate Laboratory, Braga/Guimares, Portugal


Author to whom correspondence should be addressed.

Received: 12 March 2019 / Revised: 15 April 2019 / Accepted: 23 April 2019 / Published: 29 April 2019


MDPI and ACS Style

Pereira, I.M.; Marote, A.; Salgado, A.J.; Silva, N.A. Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury. Pharmaceuticals 2019, 12, 65.

Pereira IM, Marote A, Salgado AJ, Silva NA. Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury. Pharmaceuticals. 2019; 12(2):65.

Pereira, Ins M.; Marote, Ana; Salgado, Antnio J.; Silva, Nuno A. 2019. "Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury." Pharmaceuticals 12, no. 2: 65.

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.



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Heart Disease A Closer Look at Stem Cells

By Dr. Matthew Watson

Overview of current stem cell-based approaches to treat heart disease

Since heart failure after heart attacks results from death of heart muscle cells, researchers have been developing strategies to remuscularize the damaged heart wall in efforts to improve its function. Researchers are transplanting different types of stem cell and progenitor cells (see above) into patients to repair the damaged heart muscle. These strategies have mainly used either adult stem cells (found in bone marrow, fat, or the heart itself) or pluripotent (ES or iPS) cells.

Preliminary results from experiments with adult stem cells showed that they appeared to improve cardiac function even though they died shortly after transplantation. This led to the idea that these cells can release signals that can improve function without replacing the lost muscle. Clinical trials began in the early 2000s transplanting adult stem cells from the bone marrow and then from the heart. These trials demonstrated that transplanting cells into damaged hearts is feasible and generally safe for patients. However, larger trials that were randomized, blinded, and placebo-controlled, showed fewer indications of improved function. The consensus now is that adult stem cells have modest, if any, benefit to cardiac function.

Research shows that pluripotent stem cell-derived cardiomyocytes can form beating human heart muscle cells that both release the necessary signals and replace muscle lost to heart attack. Transplantation of pluripotent stem cell-derived cardiac cells have demonstrated substantial benefits to cardiac function in animal models of heart disease, from mice to monkeys. Recently, pluripotent stem cell-derived interventions were used in clinical trials for the first time. Patches of human heart muscle cells derived from the stem cells were transplanted onto the surface of failing hearts. Early results suggest that this approach is feasible and safe, but it is too early to know whether there are functional benefits.Research is ongoing to test cellular therapies to treat heart attacks by combining different types of stem cells, repeating transplantations, or improving stem cell patches. Clinical trials using these improved methods are currently targeted to begin around 2020.Unfortunately, many unscrupulous clinics are making unsubstantiated claims about the efficacy of stem cell therapies for heart failure, creating confusion about the current state of cellular approaches for heart failure. To learn more about warning signs of these unproven interventions, please visit Nine Things to Know About Stem Cell Treatments.

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Heart Disease A Closer Look at Stem Cells

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Stem Cells for Skin Quality –

By Dr. Matthew Watson

Stem cells can do a lot of things - they can heal damaged tissue, reduce inflammation and restore function to damaged tissues. Did you know that stem cells can also improve your skin's quality and reduce the signs of aging? Innovations Stem Cell Center offers fat stem cell therapy for not only a wide array of medical conditions, but also for powerful anti-aging benefits.

How Can Stem Cell Therapy Improve Skin Quality?

Stem cells can help improve skin quality by helping to heal tissues that have been damaged by:

Aging. The aging process causes the breakdown of skin cells and skin quality, leaving the skin looking dull and dirty. Skin also loses elasticity and tightness.

Genetics. Genetics plays a large part in how your skin ages, and it's hard to fight it with over-the-counter products and treatments.

Poor diet. Lack of quality nutrition can negatively impact both the body and the skin. When the skin is not supported through a healthy diet, skin becomes dull, drab and damaged.

Environment. Environmental factors that affect the skin include pollution, dirt and germs. These things clog the pores, dull your appearance and lead to blemishes, acne and breakouts. Environmental factors also include prolonged exposure to the sun, which can cause pigmentation problems and destroy collagen and elastin.

How Is Stem Cell Therapy Used for the Skin?

One of the ways stem cell therapy is used for the skin is through a stem cell face-lift procedure. During this treatment, Dr. Johnson harvests stem cells from unwanted fat taken from another area of your body, such as your lower back or abdomen.

After the cells are harvested, they are separated from the blood and other tissue and then injected into your face with tiny needles.

The stem cell face-lift can be combined with other procedures, such as the facial fat transfer. Combining the procedures increases the odds of stem cell survival and boosts the anti-aging benefits.

What Are the Benefits of Stem Cell Therapy for the Skin?

Patients who undergo stem cell therapy for anti-aging benefits see changes in their skin such as:

Are you interested in learning more about stem cell therapy and its benefits for your skin? Call Innovations Stem Cell today at 214-256-1462 to learn more.

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Stem Cells for Skin Quality -

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A First-in-Human, Phase I Study of Neural Stem Cell …

By Dr. Matthew Watson

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Highlights

NSI-566 grafted injured spines in rats with near complete cavity-filling

The differentiation profile of grafted cells showed all three neural lineage cells

High-density human axonal sprouting was seen throughout the NSI-566 grafted region

NSI-566 transplanted in the spinal injury site of patients can be performed safely

We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (1827months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and earlysigns of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.

spinal cord injury


stem cell therapy

spinal surgery

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2018 Elsevier Inc.

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CloneR hPSC Cloning Supplement – Stemcell Technologies

By Dr. Matthew Watson

'); jQuery('.cart-remove-box a').on('click', function(){ link = jQuery(this).attr('href'); jQuery.ajax({ url: link, cache: false }); jQuery('.cart-remove-box').remove(); setTimeout(function(){window.location.reload();}, 800); }); }); //jQuery('#ajax_loader').hide(); // clear being added addToCartButton.text(defaultText).removeAttr('disabled').removeClass('disabled'); addToCartButton.parent().find('.disabled-blocker').remove(); loadingDots.remove(); clearInterval(loadingDotId); jQuery('body').append(""); setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); }); } try { jQuery.ajax( { url : url, dataType : 'json', type : 'post', data : data, complete: function(){ if(jQuery('body').hasClass('product-edit') || jQuery('body').hasClass('wishlist-index-configure')){ jQuery.ajax({ url: "", cache: false }).done(function(html){ jQuery('header#header .top-cart').replaceWith(html); }); jQuery('#ajax_loader').hide(); jQuery('body').append(""); setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); } }, success : function(data) { if(data.status == 'ERROR'){ jQuery('body').append(''); }else{ ajaxComplete(); } } }); } catch (e) { } // End of our new ajax code this.form.action = oldUrl; if (e) { throw e; } } }.bind(productAddToCartForm); productAddToCartForm.submitLight = function(button, url){ if(this.validator) { var nv = Validation.methods; delete Validation.methods['required-entry']; delete Validation.methods['validate-one-required']; delete Validation.methods['validate-one-required-by-name']; if (this.validator.validate()) { if (url) { this.form.action = url; } this.form.submit(); } Object.extend(Validation.methods, nv); } }.bind(productAddToCartForm); function setAjaxData(data,iframe,name,image){ if(data.status == 'ERROR'){ jQuery('body').append(''); }else{ if(data.sidebar && !iframe){ if(jQuery('.top-cart').length){ jQuery('.top-cart').replaceWith(data.sidebar); } if(jQuery('.sidebar .block.block-cart').length){ if(jQuery('#cart-sidebar').length){ jQuery('#cart-sidebar').html(jQuery(data.sidebar).find('#mini-cart')); jQuery('.sidebar .block.block-cart .subtotal').html(jQuery(data.sidebar).find('.subtotal')); }else{ jQuery('.sidebar .block.block-cart p.empty').remove(); content = jQuery('.sidebar .block.block-cart .block-content'); jQuery('').appendTo(content); jQuery('').appendTo(content); content.find('#cart-sidebar').html(jQuery(data.sidebar).find('#mini-cart').html()); content.find('.actions').append(jQuery(data.sidebar).find('.subtotal')); content.find('.actions').append(jQuery(data.sidebar).find('.actions button.button')); } cartProductRemove('#cart-sidebar li.item a.btn-remove', { confirm: 'Are you sure you would like to remove this item from the shopping cart?', submit: 'Ok', calcel: 'Cancel' }); } jQuery.fancybox.close(); jQuery('body').append(''); }else{ jQuery.ajax({ url: "", cache: false }).done(function(html){ jQuery('header#header .top-cart').replaceWith(html); jQuery('.top-cart #mini-cart li.item a.btn-remove').on('click', function(event){ event.preventDefault(); jQuery('body').append('Are you sure you would like to remove this item from the shopping cart?OkCancel'); jQuery('.cart-remove-box a').on('click', function(){ link = jQuery(this).attr('href'); jQuery.ajax({ url: link, cache: false }); jQuery('.cart-remove-box').remove(); setTimeout(function(){window.location.reload();}, 800); }); }); jQuery.fancybox.close(); jQuery('body').append(''); }); } } setTimeout(function () {jQuery('.add-to-cart-success').slideUp(500)}, 5000); } //]]> CloneR is a defined, serum-free supplement designed to increase the cloning efficiency and single-cell survival of human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). CloneR enables the robust generation of clonal cell lines without single-cell adaptation, thus minimizing the risk of acquiring genetic abnormalities.

CloneR is compatible with the TeSR family of media for human ES and iPS cell maintenance as well as your choice of cell culture matrix.


Greatly facilitates the process of genome editing of human ES and iPS cells Compatible with any TeSR maintenance medium and your choice of cell culture matrix Does not require adaptation to single-cell passaging Increases single-cell survival at clonal density across multiple human ES and iPS cell lines

Cell Type:

Pluripotent Stem Cells


Cell Culture

Area of Interest:

Cell Line Development; Stem Cell Biology; Disease Modeling


Defined; Serum-Free

Document Type

Product Name

Catalog #

Lot #


This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Research Area Workflow Stages for

Workflow Stages

Figure 1. hPSC Single-Cell Cloning Workflow with CloneR

On day 0, human pluripotent stem cells (hPSCs) are seeded as single cells at clonal density (e.g. 25 cells/cm2) or sorted at 1 cell per well in 96-well plates in TeSR (mTeSR1 or TeSR-E8) medium supplemented with CloneR. On day 2, the cells are fed with TeSR medium containing CloneR supplement. From day 4, cells are maintained in TeSR medium without CloneR. Colonies are ready to be picked between days 10 - 14. Clonal cell lines can be maintained long-term in TeSR medium.

Figure 2. CloneR Increases the Cloning Efficiency of hPSCs and is Compatible with Multiple hPSC Lines and Seeding Protocols

TeSR medium supplemented with CloneR increases hPSC cloning efficiency compared with cells plated in TeSR containing ROCK inhibitor. Cells were seeded (A) at clonal density (25 cells/cm2) in mTeSR1 and TeSR-E8 and (B) by single-cell deposition using FACS (seeded at 1 cell/well) in mTeSR1.

Figure 3. CloneR Increases the Cloning Efficiency of hPSCs at Low Seeding Densities

hPSCs plated in mTeSR1 supplemented with CloneR demonstrated significantly increased cloning efficiencies compared to cells plated in mTeSR1 containing ROCK inhibitor (10M Y-27632). Shown are representative images of alkaline phosphatase-stained colonies at day 7 in individual wells of a 12-well plate. H1 human embryonic stem (hES) cells were seeded at clonal density (100 cells/well, 25 cells/cm2) in mTeSR1 supplemented with (A) ROCK inhibitor or (B) CloneR on Vitronectin XF cell culture matrix.

Figure 4. CloneR Yields Larger Single-Cell Derived Colonies

hPSCs seeded in mTeSR1 supplemented with CloneR result in larger colonies than cells seeded in mTeSR1 containing ROCK inhibitor (10M Y-27632). Shown are representative images of hPSC clones established after 7 days of culture in mTeSR1 supplemented with (A) ROCK inhibitor or (B) CloneR.

Figure 5. Clonal Cell Lines Established Using CloneR Display Characteristic hPSC Morphology

Clonal cell lines established using mTeSR1 or TeSR-E8 medium supplemented with CloneR retain the prominent nucleoli and high nuclear-to-cytoplasmic ratio characteristic of hPSCs. Representative images at passage 7 after cloning are shown for clones derived from the parental (A) H1 hES cell and (B) WLS-1C human induced pluripotent stem (iPS) cell lines.

Figure 6. Clonal Cell Lines Established with CloneR Express High Levels of Undifferentiated Cell Markers

hPSC clonal cell lines established using mTeSR1 supplemented with CloneR express comparable levels of undifferentiated cell markers, OCT4 (Catalog #60093) and TRA-1-60 (Catalog #60064), as the parental cell lines. (A) Clonal cell lines established from parental H1 hES cell line. (B) Clonal cell lines established from parental WLS-1C hiPS cell line. Data is presented between passages 5 - 7 after cloning and is shown as mean SEM; n = 2.

Figure 7. Clonal Cell Lines Established Using CloneR Display a Normal Karyotype

Representative karyograms of clones derived from parental (A) H1 hES cell and (B) WLS-1C hiPS cell lines demonstrate that the clonal lines established with CloneR have a normal karyotype. Cells were karyotyped 5 passages after cloning, with an overall passage number of 45 and 39, respectively.

Figure 8. Clonal Cell Lines Established Using CloneR Display Normal Growth Rates

Fold expansion of clonal cell lines display similar growth rates to parental cell lines. Shown are clones (red) and parental cell lines (gray) for (A) H1 hES cell and (B) WLS-1C hiPS cell lines.


Internal Search Keywords: genome editing | cloning | CRISPR | clone | gene editing | 05888 | 5888 | single cell | accutase

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Bone marrow mesenchymal stem cells: Aging and tissue …

By Dr. Matthew Watson

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.



Stem cell niche

Bone healing


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2018 Published by Elsevier Ltd.

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What Can Stem Cells Do For Your Skin? | Skeyndor Australia

By Dr. Matthew Watson

Did you know that around 10,000 skin cells are born from one stem cell? Skin cells are constantly regenerating and on average live for 21 days. They make their way up from the deepest layers of your skin where they then die protecting themselves from external aggressors. As the engine for the constant renewal of your skin it is important we nourish and protect precious stem cells so they can keep producing your best skin.

As you age the activity of stem cells decrease. This is when you start to notice those first signs of ageing; thinner and more delicate skin, sagging, wrinkles and lack of luminosity. After the age of 40, the skins regeneration cycle slows down. New skin cells take longer to reach the surface of the skin, and dead cells can take twice as long to disappear, affecting the youthful appearance of your skin.

Do skincare products and skin treatments with stem cells make sense before the age of 40?Yes!

Young skin regenerates more quickly, and to mimic this we suggest an aggressive treatment, such as a peel, which removes lots of dead skin cells at once, to thenhelp your stem cells to renew andactivate the production of new, healthy and strong skin cells more quickly. Then we recommend stem cell skin products and treatments.

How exactly does a stem cell treatment work? The answer seems simple, but it is the result of many years of scientific research to ensure proven results. At Skeyndor we can guarantee this thanks to our laboratories with more than 50 years of experience in cosmeceuticals. Thanks to our incredible scientists, who have been at the forefront of skin stem cell innovations and breakthroughs we have developed two lines that contain stem cells.

Eternal:Skeyndors Eternalrangecontains the regenerative power of liposomes, derived from apple origin stem cells.These act on your skin stem cells to produce a greater amount of vital dermal substances, filling wrinkles, firming the skin and bringing luminosity to the face.

Timeless Prodigy: Timeless Prodigy by Skeyndor is a technological jewel to globally and definitively fight against the signs of skin ageing. Its formulation contains the revitalizing power of 50 million Damascus rose stem cells and is combined with the power of 10 other active ingredients, including five growth factors, white truffle and kombucha to eliminate signs of ageing. Including wrinkles and sagging, hydrating the skin in depth to revitalize its appearance and create that youthful glow. Timeless Prodigy is exclusive to select Skeyndor Spas and Beauty Salons.

Find your closest Eternal and Timeless Prodigy stockists to see the results for yourself, click here.


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Stem Cell Basics A Closer Look at Stem Cells

By Dr. Matthew Watson

About stem cells

Stem cells are the foundation of development in plants, animals and humans. In humans, there are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types oftissue-specific(oradult)stem cells that appear during fetal development and remain in our bodies throughout life.Stem cells are defined by two characteristics:

Beyond these two things, though, stem cells differ a great deal in their behaviors and capabilities.

Embryonic stem cells arepluripotent, meaning they can generate all of the bodys cell types but cannot generate support structures like the placenta and umbilical cord.

Other cells aremultipotent,meaning they can generate a few different cell types, generally in a specific tissue or organ.

As the body develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells give rise to the specialized cells that make up the bodys organs and tissues. The stem cells that stay in your body throughout your life are tissue-specific, and there is evidence that these cells change as you age, too your skin stem cells at age 20 wont be exactly the same as your skin stem cells at age 80.

Learn more about different types of stem cellshere.

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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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Preconditioning of bone marrow-derived mesenchymal stem …

By Dr. Matthew Watson

JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Oxidative stress on transplanted bone marrow-derived mesenchymal stem cells (BMSCs) during acute inflammation is a critical issue in cell therapies. N-acetyl-L cysteine (NAC) promotes the production of a cellular antioxidant molecule, glutathione (GSH). The aim of this study was to investigate the effects of pre-treatment with NAC on the apoptosis resistance and bone regeneration capability of BMSCs. Rat femur-derived BMSCs were treated in growth medium with or without 5mM NAC for 6h, followed by exposure to 100MH2O2 for 24h to induce oxidative stress. Pre-treatment with NAC significantly increased intracellular GSH levels by up to two fold and prevented H2O2-induced intracellular redox imbalance, apoptosis and senescence. When critical-sized rat femur defects were filled with a collagen sponge containing fluorescent-labeled autologous BMSCs with or without NAC treatment, the number of apoptotic and surviving cells in the transplanted site after 3 days was significantly lower and higher in the NAC pre-treated group, respectively. By the 5th week, significantly enhanced new bone formation was observed in the NAC pre-treated group. These data suggest that pre-treatment of BMSCs with NAC before local transplantation enhances bone regeneration via reinforced resistance to oxidative stress-induced apoptosis at the transplanted site.

Acute inflammation


Cell conditioning


Local transplantation


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