Stem Cell Therapy | platelet rich fibrin glue stem cells
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Stem Cell Therapy | platelet rich fibrin glue stem cells - Video

PUBLIC RELEASE DATE:

3-Dec-2014

Contact: Glenna Picton picton@bcm.edu 713-798-4710 Baylor College of Medicine @bcmhouston

HOUSTON - (Dec. 3, 2014) - A novel mechanism - similar to how normal tissue stem cells respond to wounding - might explain why bladder cancer stem cells actively contribute to chemo-resistance after multiple cycles of chemotherapy drug treatment. Targeting this "wound response" of cancer stem cells can potentially provide a novel approach for therapeutic invention, said researchers from the National Cancer Institute-designated Dan L. Duncan Cancer Center at Baylor College of Medicine.

The results of their study appear online in the journal Nature today.

"Treatment for advanced bladder cancer is limited to surgery and chemotherapy. There are no targeted treatments available," said Dr. Keith Syson Chan, an assistant professor of molecular and cellular biology and of urology and the corresponding author on the report. "The chemotherapy response is far from ideal so the clinical goal is to advance research into this area and uncover a much more targeted approach."

Together with co-lead authors Antonina Kurtova, a graduate student in the Translational Biology and Molecular Medicine Program at Baylor, and Dr. Jing Xiao, research assistant in urology at Baylor, Chan and his team sought out to identify mechanisms underlying the development of resistance in bladder cancer that has invaded the muscles. They found that regrowth of cancer stem cells actively contributes to therapy resistance between drug treatment cycles.

"This is a paradoxical mechanism leading to resistance, one we didn't expect," said Chan. "The cancer stem cells actively regrow and respond to the induced damage or apoptosis (cell death) caused by chemotherapy in between the different cycles, similar to how normal tissue stem cells respond to wound-induced damages."

The proliferation is stimulated by the release of a metabolite (or factor) called prostaglandin E2 or PGE2 from the dying cells, which causes the cancer stem cells to repopulate tumors that were reduced in size by chemotherapy, they found.

In normal cells, this is a part of the wound repair process when PGE2 induces tissues stem cells to regrow; in cancer PGE2 ironically induces regrowth of more cancer stem cells in between chemotherapy cycles, Kurtova and Xiao said.

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'Wound response' of cancer stem cells may explain chemo-resistance in bladder cancer

Stem Cell Therapy Project
Daniel, John, Magno, Thahn, Victor, Vivian show the world just exactly what stem cells really are.

By: John Peterman

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Stem Cell Therapy Project - Video

27.11.2014 - (idw) IMBA - Institut fr Molekulare Biotechnologie der sterreichischen Akademie der Wissenschaften GmbH

Scientists at IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna have made a major advancement towards a future therapy for butterfly children. A treatment with fibroblasts generated from induced pluripotent stem cells has been highly successful in mice. The next step is to establish this method in humans. Butterfly children suffer from Epidermolysis Bullosa (EB), a debilitating skin disease. It is caused by a genetic defect that leads to a deficiency or complete lack of various structural proteins. In one particularly severe form, the protein collagen 7 is either missing or present only in insufficient amounts. If that bond is missing, the skin forms blisters or tears at the slightest mechanical pressure, leading to wounds and inflammation that require extensive treatment with creams and bandages. Often these constant lesions also lead to aggressive forms of skin cancer.

Presently there is no cure for this disease. But there are promising approaches that could lead to successful treatments in the future. One of them is a method called fibroblast injection. In this procedure, fibroblasts are injected between the layers of the skin, where they can produce the necessary collagen 7.

Researchers at IMBA under the leadership of Arabella Meixner have now been successful in developing this method to treat mice affected by EB. The individual steps of this treatment have been worked out and carefully tested in many years of laboratory work, and the results have now been published in the scientific journal Science Translational Medicine.

First the scientists returned skin cells of the diseased mice to the stem cell stage and then repaired the genetic defect, the root cause of the disease. Then the researchers transformed stem cells back into fibroblasts.

Before the repaired fibroblasts could be reintroduced into the organism, measures to prevent inflammation or rejection were necessary. In this study the researchers conducted a type of toxicity test, and the results were very promising. After several months of observation, no adverse immune reactions occurred, and the risk of skin cancer did not increase. That is an important consideration because butterfly children already have a greatly increased risk of skin cancer.

The next step is to establish this skin stem cell treatment in humans. To achieve that, the IMBA scientists intend to look for partners with clinical experience. For severe forms of Epidermolysis Bullosa, a systemic application needs to be developed to spread the cells throughout the entire body via the bloodstream to reach epithelial tissues that are more difficult to access, for example the mucous membranes in the mouth or bowels. Often in butterfly children with milder forms of the disease, only certain areas of the skin are affected. The skin stem cell therapy with local injections successfully tested on mice could lead to a valuable treatment method in the very near future.

The project conducted by IMBA scientists was initiated by the patient organization DEBRA Austria, and has had the financial support of the association and of other generous supporters since 2009. DEBRA's mission is to ensure that butterfly children receive competent specialized medical care and to promote research into options to relieve and cure EB. Further thanks also go to our funding and cooperation partners sterreichische Lotterien and FK Austria Wien.

Original publication: Wenzel et. al., iPSC-based cell therapy for Recessive Dystrophic Epidermolysis Bullosa. Science Translational Medicine. 2014.

Scientific Contact: Dr. Arabella Meixner, Research Lead Tel. +43 664 2018084 arabella.meixner@imba.oeaw.ac.at Weitere Informationen:http://www.imba.oeaw.ac.at

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Tremendous progress in the development of skin stem cell treatments for butterfly children

Patients, aged one to 12, among eight children whose transplants failed Concerns arose in 2013 after operation on fundraiser Sophie Palmer, 12 Hospital says Katie Joyce, 4, could have been saved if quicker action taken Lawyers have also accused hospital of taking too long to stop transplants Ryan Loughran, 13 months, and Muhanna al-Hayany, 4, also died last year Doctors 'regret' not stopping sooner but decision seemed right at time Seventeen months on, investigations are still ongoing into exact cause

By Steph Cockroft for MailOnline

Published: 06:45 EST, 22 November 2014 | Updated: 08:49 EST, 22 November 2014

Four cancer-stricken children died at Great Ormond Street Hospital after a series of failures in stem cell transplants at the world-renowned hospital, an inquest has heard.

The young patients, aged between one and 12, were among eight children whose transplants failed when the stem cell freezing system - used in life-saving operations - inexplicably stopped working.

Four children went on to recover. But well-known charity fundraiser Sophie Ryan Palmer, 12, one-year-old Ryan Loughran, four-year-old Katie Joyce and Muhanna al-Hayany, also four, died between July and October last year.

Katie Joyce (left) and Sophie Ryan (right) were among two of the four young patients who died after a series of failures in stem cell transplants at Great Ormond Street Hospital

The children's hospital has now admitted that Katie might have survived if it had acted more quickly to resolve the problems.

Lawyers for two of the families have also accused Great Ormond Street of taking too long to stop the transplants once concerns arose.

At an inquest into the deaths this week, the court heard that doctors were initially dumbfounded as to why the procedures suddenly started failing after a decade of success, the Guardian reports.

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Four children dead at Great Ormond Street after stem cell transplant failure

PUBLIC RELEASE DATE:

20-Nov-2014

Contact: Cristy Lytal lytal@med.usc.edu 323-442-2172 University of Southern California - Health Sciences

There are plenty of body parts that don't grow back when you lose them. Nails are an exception, and a new study published in the Proceedings of the National Academy of Sciences (PNAS) reveals some of the reasons why.

A team of USC Stem Cell researchers led by principal investigator Krzysztof Kobielak and co-first authors Yvonne Leung and Eve Kandyba has identified a new population of nail stem cells, which have the ability to either self-renew or undergo specialization or differentiation into multiple tissues.

To find these elusive stem cells, the team used a sophisticated system to attach fluorescent proteins and other visible "labels" to mouse nail cells. Many of these cells repeatedly divided, diluting the fluorescence and labels among their increasingly dim progeny. However, a few cells located in the soft tissue attached to the base of the nail retained strong fluorescence and labels because they either did not divide or divided slowly -- a known property of many stem cells.

The researchers then discovered that these slow-dividing stem cells have the flexibility to perform dual roles. Under normal circumstances, the stem cells contribute to the growth of both the nails and the adjacent skin. However, if the nail is injured or lost, a protein called "Bone Morphogenic Protein," or BMP, signals to the stem cells to shift their function exclusively to nail repair.

The researchers are now wondering whether or not the right signals or environmental cues could induce these nail stem cells to generate additional types of tissue -- potentially aiding in the repair of everything from nail and finger defects to severe skin injuries and amputations.

"That was very surprising discovery, since the dual characteristic of these nail stem cells to regenerate both the nail and skin under certain physiological conditions is quite unique and different from other skin stem cells, such as those of the hair follicle or sweat gland," said Kobielak.

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Nail stem cells prove more versatile than press ons

CLEVELAND -

Our bodies contain 23 pairs of them, 46 total, but if chromosomes are damaged, they can cause birth defects, disabilities, growth problems, even death.

Case Western Reserve University scientist Anthony Wynshaw-Boris is studying how to repair damaged chromosomes with the help of a recent discovery. He's taking skin cells and reprogramming them to work like embryonic stem cells, which can grow into different cell types.

"You're taking adult or a child's skin cells. You're not causing any loss of an embryo, and you're taking those skin cells to make a stem cell," said Wynshaw-Boris.

Scientists studied patients with a specific defective chromosome that was shaped like a ring. They took the patients' skin cells and reprogrammed them into embryonic-like cells in the lab. They found this process caused the damaged "ring" chromosomes to be replaced by normal chromosomes.

"It at least raises the possibility that ring chromosomes will be lost in stem cells," said Wynshaw-Boris.

While this research was only conducted in lab cultures on the rare ring-shaped chromosomes, scientists hope it will work in patients with common abnormalities like Down syndrome.

"What we're hoping happens is we might be able to use, modify, what we did, to rescue cell lines from any patient that has any severe chromosome defect," Wynshaw-Boris explained.

It's research that could one day repair faulty chromosomes and stop genetic diseases in their tracks.

The reprogramming technique that transforms skin cells to stem cells was so groundbreaking that a Japanese physician won the Nobel Prize in medicine in 2012 for developing it.

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Health Beat: Stem cells to repair broken chromosomes

By Estel Grace Masangkay

A team of researchers at the Washington University School of Medicine in St. Louis reported that they have discovered a way to directly convert human skin cells into a type of brain cell that has been damaged by Huntingtons disease.

The team chose to produce a certain type of brain cell known as medium spiny neurons, which play a key part in controlling movement. Medium spiny neurons are the cells most affected by Huntingtons disease, a neurodegenerative disorder characterized by involuntary muscle movements and cognitive decline. The disease symptoms typically begin showing in mid-adulthood, and they steadily worsen over time.

For their experiment, the scientists used adult human skin cells instead of the typical mouse cells or embryonic human cells. The team placed the skin cells in an environment similar to the environment of brain cells and then exposed them to two small molecules of RNA named miR-9 and miR-124. In their past research, the scientists have discovered that these microRNAs turn skin cells into a mix of various neuron types. Dr. Yoo and his colleagues fine-tuned the chemical signals by further exposing the cells to transcription factors they knew are found in the part of the brain where medium spiny neurons thrive. Results show that the converted cells survived for at least six months after they were injected into mices brains. The cells also behaved in a similar fashion to native brain cells.

Not only did these transplanted cells survive in the mouse brain, they showed functional properties similar to those of native cells. These cells are known to extend projections into certain brain regions. And we found the human transplanted cells also connected to these distant targets in the mouse brain. That's a landmark point about this paper, said Dr. Andrew S. Yoo, assistant professor of developmental biology in Washington University School of Medicine and senior author of the study.

The new process differs from other techniques in that it does not need to undergo a stem cell phase, thereby avoiding production of multiple cell types. The scientists added that using adult human cells offers the opportunity to use the patients own cells in future procedures, which would radically minimize the risk of rejection by the patients immune system. Dr. Yoos team is now preparing to test skin cells taken from patients with Huntingtons disease using the approach. They also intend to inject healthy reprogrammed human cells into mice models of Huntingtons disease to check whether these have any effect on the diseases symptoms.

The researchers work was published in the previous months issue of the journal Neuron.

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Researchers Convert Skin Cells To Replace HD-Damaged Brain Cells

A large-scale trial conducted in India has shown that stem cell therapy does not work in stroke patientsREUTERS

A study conducted on 120 patients in India has shown that stem cell treatment is not effective in treating paralysis resulting from a stroke.

The research which is thefirst large-scale study conducted in Indiacompared outcomes in those treated with stem cells to others and found no difference, reports Down to Earth.

While 60 patients with some form of disability of limbs caused by a stroke were given conventional treatment, an equal number received bone marrow stem cells in addition. All had experienced a stroke 3-4 weeks before the trial.

"We found that at the end of the first month, patients with stem cells showed more improvement compared to the control group. But at the end of the third month and one year, there was no difference," said Kameshwar Prasad, head, Department of Neurology, All India Institute of Medical Sciences (AIIMS), who led the study.

On an average 280 million bone marrow cells were injected, of which blood forming stem cells were around 2.9 million per patient.

The average age of patients in the study was around 50.

The study, published in the current issue of American journal Stroke, was conducted at AIIMS in New Delhi and four other hospitals covering four cities.

The study comes when many others have been suggesting that stem cells could help treat paralysis in stroke patients. The earlier study was done on a small number of patients as compared to the AIIMs study.

More research needs to be done, before stem cells are used in therapy as in India, many private clinics are openly offering stem cell treatment for various diseases.

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Stem Cells Treatment Not Useful In Stroke Patients Finds Indian Study

I have to admit that my first response to these reports out of Britain that stem cells had been successfully used to repair a complete spinal cord transection was skepticism incredulity even. Theyre reporting that a man with a completely severed spinal cord at level T10-T11 is able to walk again! The Guardian gushes! The Daily Mail gets in the act (always a bad sign)! When I read that the patient had an 8mm gap in his spinal cord that had been filling up with scar tissue for the last two years, I was even more doubtful: under the best of conditions, it was unlikely that youd get substantial connectivity across that distance.

So I read the paper. Im less skeptical now, for a couple of reasons. They actually did this experiment on 3 people, and all showed degrees of improvement, although the newspapers are all focusing on just the one who had the greatest change. The gradual changes are all documented thoroughly and believably. And, sad to say, the improvements in the mans motor and sensory ability are more limited and more realistic than most of the accounts would have you think.

The story is actually in accord with what weve seen in stem cell repair of spinal cord injury in rats and mice.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced scientists are often reassured by this sort of dose response, as it suggests a real underlying biologically plausible effect. So the good news is that stem cell therapy does indeed seem to confer a statistically significant improvement over the residual ability of the animals both to move and feel things beyond the spinal injury site.

Significant but far from complete improvement is exactly what wed expect, and that improvement is a very, very good thing. It is an accomplishment to translate animal studies into getting measurable clinical improvements in people.

The basic procedure is straightforward. There is a population of neural cells in humans that do actively and continuously regenerate: the cells of the olfactory bulb. So what they did is remove one of the patients own olfactory bulbs, dissociate it into a soup of isolated cells, and inject them into locations above and below the injury. They also bridged the gap with strips of nerve tissue harvested from the patients leg. The idea is that the proliferating cells and the nerves would provide a nerve growth-friendly environment and build substrate bridges that would stimulate the damaged cells and provide a path for regrowth.

Big bonus: this was an autologous transplant (from the patients own tissues), so there was no worry about immune system rejection. There were legitimate worries about inflammation, doing further damage to the spinal cord, and provoking greater degeneration, and part of the purpose of this work was to assess the safety of the procedure. There were no complications.

Also, Im sure you were worried about this, but the lost olfactory cells also regenerated and the patients completely recovered their sense of smell.

Now heres the clinical assessment. Three patients were operated on; T1 is the one who has made all the news with the most remarkable improvement. There were also three control patients who showed no improvement over the same period.

Neurological function improved in all three transplant recipients (T1, T2, T3) during the first year postsurgery. This included a decrease of muscle spasticity (T1, T2) as well as improvement of sensory (T1, T2, T3) and motor function (T1, T2, T3) below the level of spinal cord injury.

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Stem cell treatment of spinal cord injuries

Stem Cell Therapy for Labrador Retriever with Ruptured Tendon
Marc Smith DVM of Natchez Trace Veterinary Services and Pet-Tao Pet Foods explains how he utilizes VetraGenics Stem Cell Therapy to regenerate tissue and heal the tendon.

By: Marc Smith

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Stem Cell Therapy for Labrador Retriever with Ruptured Tendon - Video

CHENNAI: It is harder for natives of Tamil Nadu to find a matching donor for a stem cell transplant compared to other states in the country. The suspected villain: Their genes.

A study published recently in British medical journal 'The Lancet' found that the likelihood of finding a matching stem cell donor for patients with blood-related problems in Tamil Nadu is 44.2% provided the registry had 10 lakh donors. The situation is the opposite in Haryana, with people in that state having the best chances (81.2%) of finding a donor.

Experts say consanguineous marriages are to blame. Consanguineous marriages increase the chances of patients finding a match within their small community but limit the possibility of finding one from a general donor pool.

"Unlike in other countries, stem cell variation in India is complex and dependent on ethnic variation," said Dr Dolly Daniel, professor of the department of transfusion medicine at Christian Medical College, Vellore, who was party of the study team. "Our aim was to find the size and genetic composition of each region and its impact on the proportion of patients who will be able to ?nd a suitable match."

She said Tamil Nadu could be at the tail-end of the list of states they surveyed because of inbreeding and a limited number of donors.

Stem cells are used to regenerate and repair diseased or damaged tissues. Adult stem cells are drawn from bone marrow, blood and the umbilical cord and are used to treat blood-related ailments like leukemia, thalassemia and as well as immunodeficiency.

The possibility of finding a matching stem cell donor within the family is around 30%.

"Finding a matching stem cell donor for the remaining 70% is a complex process. Most seek a graft from registries of unrelated adult donors or banked umbilical cord blood units," said Dr P Srinivasan, co-founder and chairman of Jeevan Stem Cell Bank.

Although the India stem cell industry is estimated to touch $540 million (Rs 3,250 crore) by 2015, the study noted that in terms of the number of donors, India has lagged in meeting demand. The study surveyed 10 adult donor and umbilical cord bank registries and clinical transplant centres in India and studied stem cells of 26 239 individuals.

The possibility of finding a perfect match within India is an average of 14.4% for a registry size of 25,000 and touches 60.6% for a size of 10 lakh. Registries in the country currently have around 1 lakh donors. The study said only when Indian registries have more than 2 lakh donors would patients have a good chance of finding the right match.

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Toughest for Tamil Nadu patients to get donor stem cells

The Binding of Isaac: Rebirth Unlimited Fart Sound Glitch
I played the FART SNDS seed and a bug happened, ED, or tyrone... Tyrone is a black name but he is Hispanic but appears to be white skin... Stem Cells The Binding of Isaac: Rebirth https://store.so...

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The Binding of Isaac: Rebirth Unlimited Fart Sound Glitch - Video

Magnifisio dashed home strongly over 1400m to win Saturdays Lee-Steere Stakes at Ascot. Picture: Westernracepix

Sprinter Smoko will have stem cell therapy at Murdoch Veterinary Hospital to a strained suspensory ligament in his off-foreleg.

Vets found Smoko had strained the ligament when he pulled up sore following his shock sixth as a $2 favourite to Shining Knight in last Tuesday's Colonel Reeves Stakes (1100m) at Ascot.

Co-trainer Ross Price said Smoko would be sidelined for months.

"He will go to Murdoch where they will look at him and see about stem cell therapy," he said.

"In about 10 days we will take him up there and see what they can do. It is then going to be five months off and hoping."

Smoko was a $6.50 chance in Saturday week's Winterbottom Stakes (1200m) before he was scratched. WA's hopes of winning back the Group 1 weight-for-age hinge on Magnifisio, Shining Knight and Testamezzo, with Barakey in doubt after struggling to recover from a virus.

"He is still feeling flat and I will have to wait and see if he improves over the next few days," trainer Jim Taylor said.

Magnifisio firmed from $12 into $8 on the TAB yesterday following her strong win at her debut over 1400m in Saturday's Group 2 Lee-Steere Stakes at Ascot.

Melbourne sprinters Angelic Light, Moment Of Change and reigning champion Buffering dominate betting at $4.30, $6.50 and $7.50.

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Stem cell therapy for sidelined star Smoko

Stem Cell Therapy for Multiple Sclerosis: Ron McGill
Ron McGill suffers from relapsing-remitting multiple sclerosis. He was started experiencing symptoms in 2009 but was not diagnosed with MS until January of 2013. He received several infusion...

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Stem Cell Therapy for Multiple Sclerosis: Ron McGill - Video

Enliven: Journal of Anesthesiology and Critical Care Medicine ISSN : 2374 - 4448 I e001
Left Ventricular Assist Device and Resident Cardiac Stem Cells in Heart Failure: Human Heart #39;s Potential Matter.

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Enliven: Journal of Anesthesiology and Critical Care Medicine ISSN : 2374 - 4448 I e001 - Video

TIME Health HIV/AIDS It May Be Possible To Prevent HIV Even Without a Vaccine "We're removing the doorway that HIV uses to get into cells"

Natural immunity is the most reliable way to protect yourself from viruses, bacteria and parasites. And the best way to acquire such immunity, in most cases, is to expose your immune system to the bug in questioneither by getting infected or getting immunized.

Until now, such protection was only possible with diseases like chicken pox or polio. But now, scientists at Harvard University say that people might soon arm themselves against HIV in a similar way, but through a different method.

Chad Cowan and Derrick Rossi, both in the department of stem cell and regenerative biology at Harvard University, and their colleagues report in the journal Cell Stem Cell that they have successfully edited the genomes of blood cells to make them impervious to HIV. In order survive, HIV needs to insert its genome into that of a healthy cell, and to infect these cells, HIV latches onto a protein on their surface called CCR5. If CCR5 is mutated, however, its as if the locks have been changed and HIV no longer has the right key; it cant attach itself and the cells are protected from infection. So the scientists tried a new gene editing technique called CRISPR that allows them to precisely snip out parts of a cells genome, and they spliced out the CCR5 gene. To their surprise, the technique was relatively efficient, transforming about half of the cells they treated with CRISPR into CCR5-free, or HIV-resistant, cells.

It was stunning to us how efficient CRISPR was in doing the genome editing, says Cowan.

Scientists have previously used CRISPR to make another change in how HIV infects cells; they snipped out the HIV genes that the virus inserted into healthy cells. That process essentially returned HIV infected cells back to healthy ones.

The latest results, however, suggest that the technique may be useful even before HIV gets inside cells. CRISPR could be useful in treating HIV patients if it can replace patients own immune cells with the blockaded versions. The cells Cowan and Rossi used were blood stem cells, which give rise to the bodys entire blood and immune system. In order to work as a potential treatment for HIV, patients would provide a sample of blood stem cells from their bone marrow, which would be treated with CRISPR to remove the CCR5 gene, and these cells would be transplanted back to the patient. Since the bone marrow stem cells populate the entire blood and immune system, the patient would eventually have blood cells that were protected, or immunized, against HIV. Were removing the doorway that HIV uses to get into cells, says Cowan.

To test this idea, they are already working with another research group to see if the HIV-impervious cells can treat mice infected with HIV.

Because healthy cells would be barricaded from HIV, the process might also lead to a cure for the disease. While the results are currently being tested to treat animals already infected with HIV, it may also be possible to one day transform a persons immune cell genomes to be protected against the virus. Some people are already fortunate enough to be protected this waya small percentage of people of European ancestry have natural immunity against HIV because they have two copies of mutated CCR5. They have been well studied and so far, their CCR5 aberrations dont seem to be linked to any known health issues. They are totally normal except for the fact that they are resistant to HIV, says Cowan. Thats a heartening thing: to have a group of people who are alive today who have been studied and looked at and seem totally fine.

Thats why clinicians who research the virus and treat HIV patients are excited by the possibilities of CRISPR-aided strategies. If its possible to close the door on HIV, then it may be realistic to start thinking about closing the door on the AIDS epidemic in the near future.

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It May Be Possible To Prevent HIV Even Without a Vaccine

PUBLIC RELEASE DATE:

6-Nov-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation @nyscf

New York, NY (November 6, 2014) - A team led by New York Stem Cell Foundation (NYSCF) Research Institute scientists conducted a study comparing induced pluripotent stem (iPS) cells and embryonic stem cells created using somatic cell nuclear transfer (SCNT). The scientists found that the cells derived from these two methods resulted in cells with highly similar gene expression and DNA methylation patterns. Both methods also resulted in stem cells with similar amounts of DNA mutations, showing that the process of turning an adult cell into a stem cell introduces mutations independent of the specific method used. This suggests that both methods of producing stem cells need to be further investigated before determining their suitability for the development of new therapies for chronic diseases.

The NYSCF Research Institute is one of the only laboratories in the world that currently pursues all forms of stem cell research including SCNT and iPS cell techniques for creating stem cells. The lack of laboratories attempting SCNT research was one of the reasons that the NYSCF Research Institute was established in 2006.

"We do not yet know which technique will allow scientists to create the best cells for new cellular therapies," said Susan L. Solomon, NYSCF CEO and co-founder. "It is critical to pursue both SCNT and iPS cell techniques in order to accelerate research and bring new treatments to patients."

While both techniques result in pluripotent stem cells, or cells that can become any type of cell in the body, the two processes are different. SCNT consists of replacing the nucleus of a human egg cell or oocyte with the nucleus of an adult cell, resulting in human embryonic stem cells with the genetic material of the adult cell. In contrast, scientists create iPS cells by expressing a few key genes in adult cells, like a skin or blood cell, causing the cells to revert to an embryonic-like state. These differences in methods could, in principle, result in cells with different properties. Advances made earlier this year by NYSCF Research Institute scientists that showed that human embryonic stem cells could be derived using SCNT revived that debate.

"Our work shows that we now have two methods for the generation of a patient's personal stem cells, both with great potential for the development of treatments of chronic diseases. Our work will also be welcome news for the many scientists performing basic research on iPS cells. It shows that they are likely working with cells that are very similar to human embryonic stem cells, at least with regard to gene expression and DNA methylation. How the finding of mutations might affect clinical use of stem cells generated from adult cells is the subject of an ongoing debate," said Dr. Dieter Egli, NYSCF Senior Research Fellow, NYSCF - Robertson Investigator, Assistant Professor in Pediatrics & Molecular Genetics at Columbia University, and senior author on the paper.

The study, published today in Cell Stem Cell, compared cell lines derived from the same sources using the two differing techniques, specifically contrasting the frequency of genetic coding mutations seen and measuring how closely the stem cells matched the embryonic state through the analysis of DNA methylation and of gene expression patterns. The scientists showed that both methods resulted in cell types that were similar with regard to gene expression and DNA methylation patterns. This suggested that both methods were effective in turning a differentiated cell into a stem cell.

The scientists also showed that cells derived using both SCNT and iPS techniques showed similar numbers of genetic coding mutations, implying that neither technique is superior in that regard. A similar number of changes in DNA methylation at imprinted genes (genes that are methylated differentially at the maternal versus the paternal allele) were also found. It is important to note that both types of techniques led to cells that had more of these aberrations than embryonic stem cells derived from an unfertilized human oocyte, or than embryonic stem cells derived from leftover IVF embryos. These findings suggest that a small number of defects are inherent to the generation of stem cells from adult differentiated cells and occur regardless of the method used.

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Scientists find that SCNT derived cells and IPS cells are similar

45 minutes ago by Nicole Giese Rura

Induced neural stem cells (iNSCs) created from adult cells hold promise for therapeutic transplantation, but their potential in this capacity has been limited by failed efforts to maintain such cells in the desirable multi-potent NSC state without continuous expression of the transcription factors used initially to reprogram them.

Now, Whitehead Institute scientists have created iNSCs that remain in the multi-potent state without ongoing expression of reprogramming factors. This allows the iNSCs to divide repeatedly to generate cells in quantities sufficient for therapy.

"Therapeutically, it's important to make neural stem cells because they can self-renew and make lots of cells," says Whitehead Institute Founding Member Rudolf Jaenisch, who is also a professor of biology at MIT. "If you just make mature neurons, which has been done by others, you never get enough cells."

To make iNSCs via direct lineage conversion researchers use viruses to insert a cocktail of transcription factors into the genome of mouse adult skin cells. A drug triggers these transcription factors to turn on genes active in neural stem cells. This direct conversion, known as transdifferentiation, bypasses the step of pushing the cells first through an embryonic stem-cell-like state.

In previous research, iNSCs remained addicted to the drug and reprogramming transcription factors; if either the drug or the factors was removed, the cells revert to skin cells.

"If the reprogramming factors are still active, it's horrible for the cells," says John Cassady, a scientist in Jaenisch's lab. "The cells would be unable to differentiate and the resulting cells would not be therapeutically useful."

In a paper published online this week in the current issue of the journal Stem Cell Reports, Cassady and other Whitehead scientists describe how they prevented the cells' relapse without keeping the reprogramming factors active. First, the cells were grown in a special medium that selects for neural stem cells. Then, the drug is removed. Instead of reverting into skin cells, the iNSCs remain in a multi-potent state that can differentiate into neurons and glia cells. Cassady also refined the reprogramming cocktail to contain eight transcription factors, which produces iNSCs that are transcriptionally and epigenetically similar to mouse neural stem cells.

Cassady notes that a random sample of skin cells can contain neural precursor cells, which can more easily make the transition to iNSCs. To eliminate the possibility that his method might actually rely on cells having this sort of "head start", Cassady converted fully mature immune system cells called B-lymphocytes, which have a very specific genetic marker, to iNSCs. The resulting cells had the profile of their new identity as iNSCs, yet retained their B-lymphocyte genetic marker, showing that Cassady's method could indeed convert non-neural cells to iNSCs.

Although promising, all of the work to date has been conducted in mouse cells. According to Cassady, researchers should next test this protocol in human cells to see if it can successfully produce the cell populations necessary for therapeutic use.

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Direct generation of neural stem cells could enable transplantation therapy

Researchers at Wake Forest Baptist Medical Centers Institute for Regenerative Medicine have hit upon a new strategy for tissue healing: mobilizing the bodys stem cells to the site of injury. Thus harnessing the bodys natural healing powers might make in body regeneration of muscle tissue is a possibility.

Sang Jin Lee, assistant professor of Medicine at Wake Forest, and his colleagues implanted small bits of biomaterial scaffolds into the legs of rats and mice. When they embedded these scaffolds with proteins that mobilize muscle stem cells (like insulin-like growth factor-1 or IGF-1), the stem cells migrated from the muscles to the bioscaffolds and formed muscle tissue.

Working to leverage the bodys own regenerative properties, we designed a muscle-specific scaffolding system that can actively participate in functional tissue regeneration, said Lee. This is a proof-of-concept study that we hope can one day be applied to human patients.

If patients have large sections of muscle removed because of infections, tumors or accidents, muscle grafts from other parts of the body are typically used to restore at least some of the missing muscle. Several laboratories are trying the grow muscle in the laboratory from muscle biopsies that can be then transplanted back into the patient. Growing muscle on scaffolds fashioned from biomaterials have also proven successful.

Lees technique overcomes some of the short-comings of these aforementioned procedures. As Lee put it, Our aim was to bypass the challenges of both of these techniques and to demonstrate the mobilization of muscle cells to a target-specific site for muscle regeneration.

Most tissues in our bodies contain a resident stem cell population that serves to regenerate the tissue as needed. Lee and his colleagues wanted to determine if these resident stem cells could be coaxed to move from the tissue or origin, muscle in this case, and embeds themselves in an implanted scaffold.

In their first experiments, Lee and his team implanted scaffolds into the leg muscles of rats. After retrieving them several weeks later, it was clear that the muscle stem cell population (muscle satellite cells) not only migrated into the scaffold, but other stem cell populations had also taken up residence in the scaffolds. These scaffolds were also contained an interspersed network of blood vessels only 4 weeks aster transplantation.

In their next experiments, Lee and others laced the scaffolds with different cocktails of proteins to boost the stem cell recruitment properties of the implanted scaffolds. The protein that showed the most robust stem cell recruitment ability was IGF-1. In fact, IGF-1-laced scaffolds had four times the number of cells as plain scaffolds and increased formation of muscle fibers.

The protein [IGF-1] effectively promoted cell recruitment and accelerated muscle regeneration, said Lee.

For their next project, Lee would like to test the ability of his scaffolds to promote muscle regeneration in larger laboratory animals.

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