Whats the difference between adult stem cell taken from body fat and from bone marrow
Whats the difference between adult stem cell taken from body fat and from bone marrow? In conversation with Dr Alok Sharma (MS, MCh.) Professor of Neurosurgery Head of Department, LTMG Hospital...

By: Neurogen Brain and Spine Institute

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Whats the difference between adult stem cell taken from body fat and from bone marrow - Video

Abstract

Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation.

Several seminal discoveries during the past 25 years can be regarded not only as major breakthroughs for cell and developmental biology, but also as pivotal events that have substantially influenced our view of life: 1) the establishment of embryonic stem (ES) cell lines derived from mouse (108, 221) and human (362) embryos, 2) the creation of genetic mouse models of disease through homologous recombination in ES cells (360), 3) the reprogramming of somatic cells after nuclear transfer into enucleated eggs (392), and 4) the demonstration of germ-line development of ES cells in vitro (136, 164, 365). Because of these breakthroughs, cell therapies based on an unlimited, renewable source of cells have become an attractive concept of regenerative medicine.

Many of these advances are based on developmental studies of mouse embryogenesis. The first entity of life, the fertilized egg, has the ability to generate an entire organism. This capacity, defined as totipotency, is retained by early progeny of the zygote up to the eight-cell stage of the morula. Subsequently, cell differentiation results in the formation of a blastocyst composed of outer trophoblast cells and undifferentiated inner cells, commonly referred to as the inner cell mass (ICM). Cells of the ICM are no longer totipotent but retain the ability to develop into all cell types of the embryo proper (pluripotency; Fig. 1). The embryonic origin of mouse and human ES cells is the major reason that research in this field is a topic of great scientific interest and vigorous public debate, influenced by both ethical and legal positions.

Stem cell hierarchy. Zygote and early cell division stages (blastomeres) to the morula stage are defined as totipotent, because they can generate a complex organism. At the blastocyst stage, only the cells of the inner cell mass (ICM) retain the capacity to build up all three primary germ layers, the endoderm, mesoderm, and ectoderm as well as the primordial germ cells (PGC), the founder cells of male and female gametes. In adult tissues, multipotent stem and progenitor cells exist in tissues and organs to replace lost or injured cells. At present, it is not known to what extent adult stem cells may also develop (transdifferentiate) into cells of other lineages or what factors could enhance their differentiation capability (dashed lines). Embryonic stem (ES) cells, derived from the ICM, have the developmental capacity to differentiate in vitro into cells of all somatic cell lineages as well as into male and female germ cells.

ES cell research dates back to the early 1970s, when embryonic carcinoma (EC) cells, the stem cells of germ line tumors called teratocarcinomas (344), were established as cell lines (135, 173, 180; see Fig. 2). After transplantation to extrauterine sites of appropriate mouse strains, these funny little tumors produced benign teratomas or malignant teratocarcinomas (107, 345). Clonally isolated EC cells retained the capacity for differentiation and could produce derivatives of all three primary germ layers: ectoderm, mesoderm, and endoderm. More importantly, EC cells demonstrated an ability to participate in embryonic development, when introduced into the ICM of early embryos to generate chimeric mice (232). EC cells, however, showed chromosomal aberrations (261), lost their ability to differentiate (29), or differentiated in vitro only under specialized conditions (248) and with chemical inducers (224). Maintenance of the undifferentiated state relied on cultivation with feeder cells (222), and after transfer into early blastocysts, EC cells only sporadically colonized the germ line (232). These data suggested that the EC cells did not retain the pluripotent capacities of early embryonic cells and had undergone cellular changes during the transient tumorigenic state in vivo (for review, see Ref. 7).

Developmental origin of pluripotent embryonic stem cell lines of the mouse. The scheme demonstrates the derivation of embryonic stem cells (ESC), embryonic carcinoma cells (ECC), and embryonic germ cells (EGC) from different embryonic stages of the mouse. ECC are derived from malignant teratocarcinomas that originate from embryos (blastocysts or egg cylinder stages) transplanted to extrauterine sites. EGC are cultured from primordial germ cells (PGC) isolated from the genital ridges between embryonic day 9 to 12.5. Bar = 100 m. [From Boheler et al. (40).]

To avoid potential alterations connected with the growth of teratocarcinomas, a logical step was the direct in vitro culture of embryonic cells of the mouse. In 1981, two groups succeeded in cultivating pluripotent cell lines from mouse blastocysts. Evans and Kaufman employed a feeder layer of mouse embryonic fibroblasts (108), while Martin used EC cell-conditioned medium (221). These cell lines, termed ES cells, originate from the ICM or epiblast and could be maintained in vitro (Fig. 2) without any apparent loss of differentiation potential. The pluripotency of these cells was demonstrated in vivo by the introduction of ES cells into blastocysts. The resulting mouse chimeras demonstrated that ES cells could contribute to all cell lineages including the germ line (46). In vitro, mouse ES cells showed the capacity to reproduce the various somatic cell types (98, 108, 396) and, only recently, were found to develop into cells of the germ line (136, 164, 365). The establishment of human ES cell lines from in vitro fertilized embryos (362) (Fig. 3) and the demonstration of their developmental potential in vitro (322, 362) have evoked widespread discussions concerning future applications of human ES cells in regenerative medicine.

Human pluripotent embryonic stem (ES) and embryonic germ (EG) cells have been derived from in vitro cultured ICM cells of blastocysts (after in vitro fertilization) and from primordial germ cells (PGC) isolated from aborted fetuses, respectively.

Primordial germ (PG) cells, which form normally within the developing genital ridges, represent a third embryonic cell type with pluripotent capabilities. Isolation and cultivation of mouse PG cells on feeder cells led to the establishment of mouse embryonic germ (EG) cell lines (198, 291, 347; Fig. 2). In most respects, these cells are indistinguishable from blastocyst-derived ES cells and are characterized by high proliferative and differentiation capacities in vitro (310), and the presence of stem cell markers typical of other embryonic stem cell lines (see sect. ii). Once transferred into blastocysts, EG cells can contribute to somatic and germ cell lineages in chimeric animals (197, 223, 347); however, EG cells, unlike ES cells, retain the capacity to erase gene imprints. The in vitro culture of PG cells from 5- to 7-wk-old human fetuses led to the establishment of human EG cell lines (326) (Fig. 3). These cell lines showed multilineage development in vitro but have a limited proliferation capacity, and currently can only be propagated as embryoid body (EB) derivatives (325). Following transplantation into an animal model for neurorepair, human EG cell derivatives, however, show some regenerative capacity, suggesting that these cells could be useful therapeutically (190). Although pluripotent EG and EC cells represent important in vitro models for cell and developmental biology, this review focuses mainly on fundamental properties and potential applications of mouse and human ES cells for stem cell research.

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Embryonic Stem Cells: Prospects for Developmental Biology ...

An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

Sydney-based Regeneus has revealed it was recently given permission for its HiQCell treatment on players suffering from such issues as osteoarthritis and tendinopathy.

The treatment is banned by the World Anti-Doping Agency if it is performance-enhancing but allowed if it is solely to treat injuries.

Regeneus commercial development director Steven Barberasaid the regenerative medicine company had sought approval from the AFL for what the company says is "innovative but not experimental" treatment.

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"In 2013, Regeneus sought and received clearance from ASADA [Australian Sports Anti-Doping Authority] for its proprietary HiQCell therapy for use with athletes who participate in sporting competitions subject to the WADA Anti-Doping Code. The AFL is one of many professional sports bodies which applies the WADA Anti-Doping Code within its regulations for players," he said.

"In March this year, the AFL introduced a Prohibited Treatments List as an additional level of scrutiny over and above the WADA code for player treatments. In light of this, Regeneus made a submission to the AFL to confirm that our specific treatment is not prohibited under that list. Subsequently, the chief medical officer of the AFL has recently communicated with our primary Melbourne-based HiQCell medical practitioner that the treatment is not prohibited and can be administered on a case-by-case basis to players.

"We anticipate documented confirmation of this outcome in the near future from the AFL.

"To our knowledge, the permission is specific to HiQCell and not necessarily to cell-based therapies in general."

The AFL confirmed it had given approval on a "case-by-case" basis.

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AFL approves stem-cell therapy treatment

STEM CELL THERAPY CONCERTO
HEALING is the inevitable objective of stem cell rejuvenation, which is just beautiful integrative with time proven treatments such as acupuncture and entrenched with social science for the...

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STEM CELL THERAPY CONCERTO - Video

Because the ALS Association supports stem-cell research.

The Ice Bucket Challenge has been the biggest viral-charity sensation of the year, and maybe ever reaching its cold, wet arms all the way to George W. Bush and Anna Wintour, and raising millions of dollars for ALS research along with providing an immaculate blooper reel.

But one group is not pleased by all your Facebook videos: anti-abortion activists, who are mad that the ALS Association gives money to a group that supports stem-cell research.

"Attention pro-lifers: be careful where you send your ALS Ice Bucket Challenge donation," blared a headline on LifeNews.com earlier this week. The article explained that the ALS Association, one of the charities receiving ice-bucket donations, gave $500,000 last year to the Northeast ALS Consortium, which in turn had been affiliated with a clinical trial that used "stem cells ... engineered from the spinal cord of a single fetus electively aborted after eight weeks of gestation. The tissue was obtained with the mothers consent."

"Of course the fetus, from whom the 'tissue' was taken, did not 'give consent,'" LifeNews.com wrote. "So if you give to the ALS Association your money may end up supporting clinical trials that use aborted fetal cells."

Following the report, the Cincinnati Archdiocese warned Catholic school principals not to send donations to the ALS Association, andsome anti-abortion activists have begun making their own "pro-life Ice Bucket Challenge" videos.

CBN News, the Christian TV channel that broadcasts Pat Robertson's 700 Club, put a video of its Ice Bucket Challenge on Facebook, but not without informing its audience that the donations from the challenge would go to "an organization that does not support or use embryonic stem cell research."

Meanwhile, a 2013 FDA-approved study using human stem cells resulted in slowing the progression of ALS to an "extraordinary" degree.

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Anti-Abortion Activists Are Doing Their Own Ice Bucket Challenges

Released: 19-Aug-2014 11:30 AM EDT Embargo expired: 21-Aug-2014 12:00 PM EDT Source Newsroom: Johns Hopkins Medicine Contact Information

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Newswise Johns Hopkins stem cell biologists have found a way to reprogram a patients skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. The process requires growing the skin cells in a bath of proteins and chemical additives while turning on a gene to produce neural crest cells, which give rise to several adult cell types. The researchers say their work substantially expedites the creation of neural crest cells from any patient with a neural crest-related disorder, a tool that lets physicians and scientists study each patients disorder at the cellular level.

Previously, the same research team produced customized neural crest cells by first reprogramming patient skin cells into induced pluripotent stem (iPS) cells, which are similar to embryonic stem cells in their ability to become any of a broad array of cell types.

Now we can circumvent the iPS cells step, saving seven to nine months of time and labor and producing neural crest cells that are more similar to the familial dysautonomia patients cells, says Gabsang Lee, Ph.D., an assistant professor of neurology at the Institute for Cell Engineering and the studys senior author. A summary of the study will be published online in the journal Cell Stem Cell on Aug. 21.

Neural crest cells appear early in human and other animal prenatal development, and they give rise to many important structures, including most of the nervous system (apart from the brain and spinal cord), the bones of the skull and jaws, and pigment-producing skin cells. Dysfunctional neural crest cells cause familial dysautonomia, which is incurable and can affect nerves ability to regulate emotions, blood pressure and bowel movements. Less than 500 patients worldwide suffer from familial dysautonomia, but dysfunctional neural crest cells can cause other disorders, such as facial malformations and an inability to feel pain.

The challenge for scientists has been the fact that by the time a person is born, very few neural crest cells remain, making it hard to study how they cause the various disorders.

To make patient-specific neural crest cells, the team began with laboratory-grown skin cells that had been genetically modified to respond to the presence of the chemical doxycycline by glowing green and turning on the gene Sox10, which guides cells toward maturation as a neural crest cell.

Testing various combinations of molecular signals and watching for telltale green cells, the team found a regimen that turned 2 percent of the cells green. That combination involved turning on Sox10 while growing the cells on a layer of two different proteins and giving them three chemical additives to rewind their genetic memory and stimulate a protein network important for development.

Analyzing the green cells at the single cell level, the researchers found that they showed gene activity similar to that of other neural crest cells. Moreover, they discovered that 40 percent were quad-potent, or able to become the four cell types typically derived from neural crest cells, while 35 percent were tri-potent and could become three of the four. The cells also migrated to the appropriate locations in chick embryos when implanted early in development.

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Biologists Reprogram Skin Cells to Mimic Rare Disease

Durham, NC (PRWEB) August 22, 2014

Human induced pluripotent stem cells (hiPSCs) have great potential in the field of regenerative medicine because they can be coaxed to turn into specific cells; however, the new cells dont always act as anticipated. They sometimes mutate, develop into tumors or produce other negative side effects. But in a new study recently published in STEM CELLS Translational Medicine, researchers appear to have found a way around this, simply by removing the material used to reprogram the stem cell after they have differentiated into the desired cells.

The study, by Ken Igawa, M.D., Ph.D., and his colleagues at Tokyo Medical and Dental University along with a team from Osaka University, could have significant implications both in the clinic and in the lab.

Scientists induce (differentiate) the stem cells to become the desired cells, such as those that make up heart muscle, in the laboratory using a reprogramming transgene that is, a gene taken from one organism and introduced into another using artificial techniques.

We generated hiPSC lines from normal human skin cells using reprogramming transgenes, then we removed the reprogramming material. When we compared the transgene-free cells with those that had residual transgenes, both appeared quite similar, Dr. Igawa explained. However, after the cells differentiation into skin cells, clear differences were observed.

Several types of analyses revealed that the keratinocytes cells that make up 90 percent of the outermost skin layer that emerged from the transgene-free hiPSC lines were more like normal human cells than those coming from the hiPSCs that still contained some reprogramming material.

These results suggest that transgene-free hiPSC lines should be chosen for therapeutic purposes, Dr. Igawa concluded.

Human induced pluripotent stem cell (hiPSC) lines have potential for therapeutics because of the customized cells and organs that can potentially be induced from such cells, Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. This study illustrates a potentially powerful approach for creating hiPSCs for clinical use.

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The full article, Removal of Reprogramming Transgenes Improves the Tissue Reconstitution Potential of Keratinocytes Generated From Human Induced Pluripotent Stem Cells, can be accessed at http://stemcellstm.alphamedpress.org/content/early/2014/07/14/sctm.2013-0179.abstract.

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Removing Programming Material After Inducing Stem Cells Could Improve Their Regeneration Ability

what is the procedure of stem cell therapy for autism spectrum disorder
What is the procedure of stem cell therapy for autism spectrum disorder? In conversation with Dr Alok Sharma (MS, MCh.) Professor of Neurosurgery Head of Department, LTMG Hospital LTM Medical...

By: Neurogen Brain and Spine Institute

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what is the procedure of stem cell therapy for autism spectrum disorder - Video

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries -- a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

The finding that coronary arteries house a cardiac stem cell "niche" has interesting implications, Hatzopoulos said. Coronary artery disease -- the No. 1 killer in the United States -- would impact this niche.

"Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated," he said.

The current research follows a previous study in which Hatzopoulos and colleagues demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue.

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Coronary arteries hold heart-regenerating cells

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20-Aug-2014

Contact: Craig Boerner craig.boerner@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

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Vanderbilt researchers find that coronary arteries hold heart-regenerating cells

ROCHESTER, Minn. (KTTC) -- Medical officials are talking about a breakthrough clinical trial that could help the heart repair itself.

On Tuesday afternoon, Mayo Clinic and Cardio3 BioSciences officials outlined an FDA-approved clinical trial to be carried out in the United States. A similar trial has already been underway in Europe.

Cardio3 CEO Christian Homsy said stem cells are a major part of this heart-healing process. "What we do is take cells from a patient and we reprogram those cells to become cardiac reparative cells. Those cells have the ability to come and repair the heart." Those stem cells would come from the bone marrow of patients who suffer from heart failure.

This treatment is the result of a Mayo Clinic discovery. In Mayo's breakthrough process, stem cells that are harvested from a cardiac patient's bone marrow undergo a guided treatment designed to improve heart health in people suffering from heart failure.

Cardio3 officials said a manufacturing facility will be the first thing that is needed for this clinical trial, and the rest of the details like staffing will follow.

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Trial to use stem cells to repair heart

Chemotherapy and Radiation Therapy

Before you get the stem cell transplant, youll get the actual cancer treatment. To destroy the abnormal stem cells, blood cells, and cancer cells your doctor will give you high doses of chemotherapy, radiation therapy, or both. In the process, the treatment will kill healthy cells in your bone marrow, essentially making it empty. Your blood counts (number of red blood cells, white blood cells, and platelets) will drop quickly. Since chemotherapy and radiation can cause nausea and vomiting, you might need anti-nausea drugs.

Without bone marrow, your body is vulnerable. You won't have enough white blood cells to protect you from infection. So during this time, you might be isolated in a hospital room or required to stay at home until the new bone marrow starts growing. You might also need transfusions and medication to keep you healthy.

A few days after youve finished with your chemotherapy or radiation treatment, your doctor will order the actual stem cell transplant. The harvested stem cells -- either from a donor or from your own body -- are thawed and infused into a vein through an IV tube. The process is essentially painless. The actual stem cell transplant is similar to a blood transfusion. It takes one to five hours.

The stem cells then naturally move into the bone marrow. The restored bone marrow should begin producing normal blood cells after several days, or up to several weeks later.

The amount of time youll need to be isolated will depend on your blood counts and general health. When you are released from the hospital or from isolation at home, your transplant team will provide you with specific instructions on how to care for yourself and prevent infections. Youll also learn what symptoms need to be checked out immediately. Full recovery of the immune system might take months or even years. Your doctor will need to do tests to check on how well your new bone marrow is doing.

There are also variations in the stem cell transplant process being studied in clinical trials. One approach is called a tandem transplant, in which a person would get two rounds of chemotherapy and two separate stem cell transplants. The two transplants are usually done within six months of one another.

Another is called a mini-transplant, in which doctors use lower doses of chemotherapy and radiation. The treatment is not strong enough to kill all of the bone marrow -- and it wont kill all of the cancer cells either. However, once the donated stem cells take hold in the bone marrow, they produce immune cells that might attack and kill the remaining cancer cells. This is also called a non-myeloablative transplant.

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Bone Marrow Transplants and Stem Cell Transplants for ...

A team of chemical engineers from MIT has developed a new method of stimulating bone growth, by utilizing the same chemical processes that occur naturally in the human body following an injury such as a broken or fractured bone. The technique involves the insertion of a porous scaffold coated with growth factors that prompt the body's own cells to naturally mend the damaged or deformed bone.

Current techniques for replacing or mending damaged bone often include a bone transplant from another area of the patient's body. This is an expensive, painful, and often inadequate option for treatment, as it is difficult to harvest enough bone to successfully treat the wound. Due to the inadequacies of the current forms of bone replacement treatment, a number of scaffold-based approaches are in development, however few are as promising as the tissue scaffold presented by the team from MIT.

The new method would seek to mimic the natural steps taken by the human body to encourage bone growth without the unpleasant necessity of extracting further bone from the patient's body. After a break or fracture, the body releases both platelet-derived growth factors, (PDGF) and bone morphogenetic protein 2 (BMP-2), in order to stimulate natural bone regeneration. These factors essentially recruit other immature cells, coaxing them to become osteoblasts, a cell type with the capacity to create new bone. At the same time, the PDFG and BMP-2 provide a supporting structure around which the bone can be rebuilt.

The 0.1 mm-thick polymer scaffold sheet developed by the scientists from MIT would appear to successfully mimic this biological process, releasing the growth factors in the correct order and quantity, essentially tricking the body into thinking it had initiated the healing process itself. Previous attempts at biomimicry in this area have failed due to an inability to release the growth factors in a natural and controlled fashion, causing the body to clear the factors away from the wound before they could have any substantial healing effect.

The scaffold has the potential to do away with the painful, invasive procedures currently used to repair/replace bone (Image: MIT)

"You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities," States Paula Hammond, member of MIT's Koch Institute for Integrative Cancer Research and Department of Engineering, and senior author on the paper outlining the results of the study. "You want to recruit these native adult stem cells we have in our bone marrow to go to the site of injury and then generate bone around the scaffold, and you want to generate a vascular system to go with it."

The measured release of growth factors is achieved by layering the porous scaffold with around 40 layers of BMP-2, followed by another 40 layers of PDGF. Once the layering process is complete, medical practitioners can cut out segments of the scaffold, tailoring the treatment to fit any size of wound. Furthermore, once the treatment has run its course and the bone has been regrown, the biodegradable scaffold is safely adsorbed into the body, leaving no harmful traces as a by-product of the procedure.

The scaffold has been tested in the lab by administering the treatment to rats with skull deficiencies too large to be healed without the aid of outside stimuli. It was found that the initial release of the PDGF created a healing cascade, mobilizing cells important to the rebuilding process to move to the site of the deformity. The BMP-2 then went to work inducing a number of the cells to become osteoblasts, which would go on to create the new bone.

Only two weeks after the initial transplant, it was found that fresh bone had been created that was indistinguishable in nature from the natural bone found in the surrounding areas of the skull. Looking to the future, the team hopes to test the technique on larger animals, with the long-term goal of advancing to clinical trials.

A paper covering the research carried out by the team from MIT has been published in the journal Proceedings of the National Academy of Sciences of the United States of America.

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MIT scientists use polymer scaffold to stimulate bone growth

Novartis ( NVS ) recently entered into an investment and option agreement with Israel-based Gamida Cell, a company which focuses on stem cell expansion technologies and therapeutic products.

As per the terms of the agreement, Novartis will invest $35 million in Gamida Cell. In exchange, Novartis will receive a 15% stake in Gamida Cell and an option to fully acquire the company.

The option for full acquisition is exercisable for a limited period of time following achievement of certain milestones in connection with the development of pipeline candidate, NiCord. These milestones are expected to be achieved during 2015. Novartis will also be required to pay the other shareholders in Gamida Cell approximately $165 million upon exercising the option along with potential milestone payments of $435 million.

We note that Gamida Cell is developing stem cell therapy for the potential treatment of blood cancers, solid tumors, non-malignant hematological diseases such as sickle cell disease and thalassemia, neutropenia and acute radiation syndrome, autoimmune diseases and genetic metabolic diseases as well as conditions that can be helped by regenerative medicine.

The company is currently evaluating NiCord for the potential treatment of hematological malignancies such as leukemia and lymphoma in a phase I/II study using its proprietary NAM technology.

Meanwhile, enrolment is on for the company's phase I/II study on NiCord for pediatric sickle cell disease.

We remind investors that Novartis has been taking strategic steps to realign its portfolio in order to focus on its core portfolio of pharmaceuticals, eye care and generics. Novartis' recent deal to acquire oncology products from GlaxoSmithKline ( GSK ) and the divestiture of the Vaccines business is a step in the right direction.

Novartis, a large-cap pharma, currently carries a Zacks Rank #3 (Hold). Right now, Allergan ( AGN ) and AbbVie ( ABBV ) look well positioned among the large-cap pharmas. While Allergan carries a Zacks Rank #1 (Strong Buy), AbbVie is a Zacks Rank #2 (Buy) stock.

NOVARTIS AG-ADR (NVS): Free Stock Analysis Report

ABBVIE INC (ABBV): Free Stock Analysis Report

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Novartis to Invest $35M in Gamida Cell for 15% Equity - Analyst Blog

(PRWEB UK) 21 August 2014

The success of stem cell medicine does not depend on funding alone

Funding is of the upmost importance but access to the right material is vital.

Stem Cell Banking of a childs own stem cells for potentially a lifetime of use, is a way of storing their health for their future. So it is vital that the right stem cells are available for treatment when they are needed at any time in their life.

Tony Veverka, Group CEO of specialist stem cell bank BioEden says, "Funding is of the upmost importance so that research can continue, but access to the right material is vital."

Gaining access to the right material for stem cell therapy has dramatically simplified since BioEden pioneered an entirely non-invasive method of taking stem cells from children's baby teeth. No longer is there just the option of stem cells from embryos, bone marrow or cord blood, but the option of taking quality cells from the baby tooth after it has fallen out naturally.

BioEden believes it can cut NHS funding dramatically by individuals banking their own stem cells, and they continue to call for clarity and transparency so that a prolonged and healthier life is accessible to all. http://www.thetimes.co.uk/tto/business/industries/health/article4181168.ece

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The Times Have Published Only Half the Story, Says Specialist Stem Cell Bank BioEden

By Estel Grace Masangkay

With help from the zebrafish, a team of Australian researchers has uncovered how hematopoietic stem cells (HSC) renew themselves, considered by many to be the holy grail of stem cell research.

HSCs are a significant type of stem cell present in the blood and bone marrow. These are needed for the replenishment of the bodys supply of blood and immune cells. HSCs already play a part in transplants in patients with blood cancers such as leukemia and myeloma. The stem cells are also studied for their potential to transform into vital cells including muscle, bone, and blood vessels.

Understanding how HSCs form and renew themselves has potential application in the treatment of spinal cord injuries, degenerative disorders, even diabetes. Professor Peter Currie, of the Australian Regenerative Medicine Institute at Victorias Monash University, led a research team to discover a crucial part of HSCs development. Using a high-resolution microscopy, Prof. Curies team caught HSCs on film as they formed inside zebrafish embryos. The discovery was made while the researchers were studying muscle mutations in the aquatic animal.

Zebrafish make HSCs in exactly the same way as humans do, but whats special about these guys is that their embryos and larvae develop free living and not in utero as they do in humans. So not only are these larvae free-swimming, but they are also transparent, so we could see every cell in the body forming, including HSCs, explained Prof. Currie.

While playing the film back, the researchers noticed that a buddy cell came along to help the HSCs form. Called endotome cells, they aided pre-HSCs to turn into HSCs. Prof. Currie said, Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.

The next step for the researchers is to locate the signals present in the endotome cells that trigger HSC formation in the embryo. This can help scientists make different blood cells on demand for blood-related disorders. Professor Currie also pointed out the discoverys potential for correcting genetic defects in the cell and transplanting them back in the body to treat disorders.

The teams work was published in the international journal Nature.

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Stem Cell Research Holy Grail' Uncovered, Thanks to Zebrafish

Ruxolitinib (trade name: Jakavi) has been approved since August 2012 for the treatment of adults with myelofibrosis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate comparator therapy specified by the Federal Joint Committee (G-BA).

According to the results, there is an indication of considerable added benefit in comparison with "best supportive care" (BSC) because ruxolitinib is better at relieving symptoms. Moreover, a hint of an added benefit with regard to survival can be derived from the dossier. Its extent is non-quantifiable, however.

Bone marrow is replaced by connective tissue

Myelofibrosis is a rare disease of the bone marrow, in which the bone marrow is replaced by connective tissue. As a consequence of this so-called fibrosis, the bone marrow is no longer able to produce enough blood cells. Sometimes the spleen or the liver takes over some of the blood production. Then these organs enlarge and can cause abdominal discomfort and pain. The typical symptoms also include feeling of fullness, night sweats and itching. Some patients with myelofibrosis develop leukemia.

Stem cell transplantation is currently the only option to cure myelofibrosis. The drug ruxolitinib aims to relieve the symptoms of myelofibrosis.

G-BA specifies appropriate comparator therapy

Ruxolitinib is an option for patients with so-called primary or secondary myelofibrosis whose spleen is already enlarged (splenomegaly) or who have other disease-related symptoms.

The G-BA specified "best supportive care" (BSC) as appropriate comparator therapy. BSC means a therapy that provides the patient with the best possible, individually optimized, supportive treatment to alleviate symptoms and improve quality of life. This also includes adequate pain therapy.

Relevant study ongoing until 2015

In its assessment, IQWiG could include one randomized controlled trial (RCT) conducted in 89 centres in Australia, Canada and the United States (COMFORT-I). The 309 patients in total were either treated with ruxolitinib plus BSC or with placebo plus BSC.

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Ruxolitinib for myelofibrosis: Indication of considerable added benefit

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Newswise A new study by Barbara Beltz, the Allene Lummis Russell Professor of Neuroscience at Wellesley College, and Irene Sderhll of Uppsala University, Sweden, published in the August 11 issue of the journal Developmental Cell, demonstrates that the immune system can produce cells with stem cell properties, using crayfish as a model system. These cells can, in turn, create neurons in the adult animal. The flexibility of immune cells in producing neurons in adult animals raises the possibility of the presence of similar types of plasticity in other animals.

We have been suspicious for some time that the neuronal precursor cells (stem cells) in crayfish were coming from the immune system, Beltz wrote. The paper contains multiple lines of evidence that support this conclusion, in addition to the experiments showing that blood cells transferred from a donor to a recipient animal generate neurons.

Beltz, whose research focuses on the production of new neurons in the adult nervous system, uses the crustacean brain as the model system because the generations of precursor cells are spatially segregated from one another. According to Beltz, this separation is crucial because it allowed the researchers to determine that the first generation precursors do not self-renew. For the Developmental Cell study, the cells of one crayfish were labeled and this animals blood was used for transfusions into another crayfish. They found that the donor blood cells could generate neurons in the recipient.

In many adult organisms, including humans, neurons in some parts of the brain are continually replenished. While this process is critical for ongoing health, dysfunctions in the production of new neurons may also contribute to several neurological diseases, including clinical depression and some neurodegenerative disorders.

Beltz notes, of course, that it is difficult to extrapolate from crayfish to human disease. However, because of existing research suggesting that stem cells harvested from bone marrow also can become neural precursors and generate neurons, she says it is tempting to suggest that the mechanism proposed in crayfish may also be applicable in evolutionarily higher organisms, perhaps even in humans.

Prior studies conducted in both humans and mice and published about a decade ago, showed that bone marrow recipients who had received a transplant from the opposite gender had neurons with the genetic signature of the opposite sex. The implication was that cells from the bone marrow generated those neurons. However, it is currently thought that neuronal stem cells in mammals, including humans, are self-renewing and therefore do not need to be replenished. Thus, these findings have not been interpreted as contributing to a natural physiological mechanism.

Every experiment we did confirmed the close relationship between the immune system and adult neurogenesis, Beltz said. Often when one is doing research, experiments can be fussy or give variable results. But for this work, once we started asking the right questions, the experiments worked first time and every time. The consistency and strength of the data are remarkable.

Our findings in crayfish indicate that the immune system is intimately tied to mechanisms of adult neurogenesis, suggesting a much closer relationship between the immune system and nervous system than has been previously appreciated, said Sderhll. If further studies demonstrate a similar relationship between the immune system and brain in mammals, these findings would stimulate a new area of research into immune therapies to target neurological diseases.

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Blood Cells Generate Neurons in Crayfish; Could Have Implications for Treatment of Neurodegenerative Disorders

A new research has suggested that immune cells, known as natural killer cells could help in hunting down and kill cancers that have spread in the body.

The study showed that a protein called MCL-1 was vital for survival of natural killer cells.

Dr. Nick Huntington said that they discovered that MCL-1 was absolutely essential for keeping natural killer cells alive and without natural killer cells, the body was unable to destroy melanoma metastases that had spread throughout the body, and the cancers overwhelmed the lungs.

Huntington said that the natural killer cells led the response that caused rejection of donor stem cells in bone marrow transplantations and they also produced inflammatory signals that could result in toxic shock syndrome, a potentially fatal illness caused by bacterial toxins that causes a whole-body inflammatory reaction.

The study is published in the journal Nature Communications.

(Posted on 15-08-2014)

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'Killer' immune cells destroy body cancer

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Newswise A genetic variation linked to schizophrenia, bipolar disorder and severe depression wreaks havoc on connections among neurons in the developing brain, a team of researchers reports. The study, led by Guo-li Ming, M.D., Ph.D., and Hongjun Song, Ph.D., of the Johns Hopkins University School of Medicine and described online Aug. 17 in the journal Nature, used stem cells generated from people with and without mental illness to observe the effects of a rare and pernicious genetic variation on young brain cells. The results add to evidence that several major mental illnesses have common roots in faulty wiring during early brain development.

This was the next best thing to going back in time to see what happened while a person was in the womb to later cause mental illness, says Ming. We found the most convincing evidence yet that the answer lies in the synapses that connect brain cells to one another.

Previous evidence for the relationship came from autopsies and from studies suggesting that some genetic variants that affect synapses also increase the chance of mental illness. But those studies could not show a direct cause-and-effect relationship, Ming says.

One difficulty in studying the genetics of common mental illnesses is that they are generally caused by environmental factors in combination with multiple gene variants, any one of which usually could not by itself cause disease. A rare exception is the gene known as disrupted in schizophrenia 1 (DISC1), in which some mutations have a strong effect. Two families have been found in which many members with the DISC1 mutations have mental illness.

To find out how a DISC1 variation with a few deleted DNA letters affects the developing brain, the research team collected skin cells from a mother and daughter in one of these families who have neither the variation nor mental illness, as well as the father, who has the variation and severe depression, and another daughter, who carries the variation and has schizophrenia. For comparison, they also collected samples from an unrelated healthy person. Postdoctoral fellow Zhexing Wen, Ph.D., coaxed the skin cells to form five lines of stem cells and to mature into very pure populations of synapse-forming neurons.

After growing the neurons in a dish for six weeks, collaborators at Pennsylvania State University measured their electrical activity and found that neurons with the DISC1 variation had about half the number of synapses as those without the variation. To make sure that the differences were really due to the DISC1 variation and not to other genetic differences, graduate student Ha Nam Nguyen spent two years making targeted genetic changes to three of the stem cell lines.

In one of the cell lines with the variation, he swapped out the DISC1 gene for a healthy version. He also inserted the disease-causing variation into one healthy cell line from a family member, as well as the cell line from the unrelated control. Sure enough, the researchers report, the cells without the variation now grew the normal amount of synapses, while those with the inserted mutation had half as many.

We had our definitive answer to whether this DISC1 variation is responsible for the reduced synapse growth, Ming says.

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Stem Cells Reveal How Illness-Linked Genetic Variation Affects Neurons