Direct generation of neural stem cells could enable transplantation therapy

8 hours 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

Stem cell transplants may help reduce seizures, study says

New research from McLean Hospital and the Harvard Stem Cell Institute has shown that stem cell therapy reduces seizures in mice.

Researchers used an animal model to transplant seizure-inhibiting, human embryonic stem cell-derived neurons into the brains of mice that had a common form of epilepsy. Half of the mice that received the transplanted neurons no longer had seizures, while the other half experienced a significant drop in seizure frequency.

The transplanted neurons integrated into the mouse brains and began to receive neuronal activity. The neurons then released GABA, an inhibitory response that reversed the electrical hyperactivity that causes seizure.

Previous studies showed increasing inhibition in the epileptic brain can help control the seizure and also a lot of anti-epilepsy drugs are mimicking this GABA, so many of them worked by binding to the GABA receptors, researcher Sangmi Chung, assistant professor of psychiatry at Harvard, told FoxNews.com.

Researchers initially set out to test the functionality of human neurons, but later decided to test their effect on epilepsy because it is such a devastating disease. About 30 percent of people do not respond to seizure drugs and one out of 26 people will be affected by seizures in their lifetime, Chung said.

Over 65 million people worldwide are affected by epileptic seizures, which can cause convulsions, loss of consciousness and other neurological symptoms. Patients are treated with anti-seizure drugs, and may choose to have a portion of their brain removed.

Because mouse cells mature more quickly than human cells within weeks instead of years it was unclear how long a stem cell transplant in a human would take before becoming effective, Chung noted.

If we compare it with the mouse [model], we believe it will be years, not weeks, she said.

However, the study found that, even without full maturation, the cells integrated into the epileptic mouse brains, receive signals and release GABA, therefore preventing seizures.

I think its really good news in terms of transplantation even maturing, not fully mature [cells] still work, Chung said.

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Stem cell transplants may help reduce seizures, study says

Transplant of stem-cell-derived dopamine neurons shows promise for Parkinson's disease

PUBLIC RELEASE DATE:

6-Nov-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press @CellPressNews

Parkinson's disease is an incurable movement disorder that affects millions of people around the world, but current treatment options can cause severe side effects and lose effectiveness over time. In a study published by Cell Press November 6th in Cell Stem Cell, researchers showed that transplantation of neurons derived from human embryonic stem cells (hESCs) can restore motor function in a rat model of Parkinson's disease, paving the way for the use of cell replacement therapy in human clinical trials.

"Our study represents an important milestone in the preclinical assessment of hESC-derived dopamine neurons and provides essential support for their usefulness in treating Parkinson's disease," says senior study author Malin Parmar of Lund University.

Parkinson's disease is caused, in part, by the death of neurons that release a brain chemical called dopamine, leading to the progressive loss of control over dexterity and the speed of movement. Currently available drug and surgical treatment options can lose effectiveness over time and cause serious side effects such as involuntary movements and psychiatric problems. Meanwhile, another approach involving the transplantation of human fetal cells has produced long-lasting clinical benefits; however, the positive effects were only seen in some individuals and can also cause involuntary movements driven by the graft itself. Moreover, the use of tissue from aborted human fetuses presents logistical issues such as the limited availability of cells, hampering the effective translation of fetal tissue transplantation as a realistic therapeutic option.

To rigorously assess an alternative hESC-based treatment approach, Parmar and lead study author Shane Grealish of Lund University transplanted hESC-derived dopamine neurons into brain regions that control movement in a rat model of Parkinson's disease. The transplanted cells survived the procedure, restored dopamine levels back to normal within five months, and established the correct pattern of long-distance connections in the brain. As a result, this therapy restored normal motor function in the animals. Importantly, the hESC-derived neurons show efficacy and potency similar to fetal neurons when transplanted in the rat model of Parkinson's disease, suggesting that the hESC-based approach may be a viable alternative to the approaches that have already been established with fetal cells in Parkinson's patients.

In a related Forum article published in the same issue, Roger Barker of Addenbrooke's Hospital and the University of Cambridge laid out the roadmap for taking stem-cell-derived dopamine neurons to the clinic for treating Parkinson's disease. "This involves understanding the history of the whole field of cell-based therapies for Parkinson's disease and some of the mistakes that have happened," he says. "It also requires a knowledge of what the final product should look like and the need to get there in a collaborative way without being tempted to take shortcuts, because a premature clinical trial could impact negatively on the whole field of regenerative medicine."

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Cell Stem Cell, Grealish et al.: "Human ESC-derived dopamine neurons show preclinical efficacy and potency similar to fetal neurons when grafted in a rat model of Parkinson's disease."

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Transplant of stem-cell-derived dopamine neurons shows promise for Parkinson's disease

Stem cells help doctors restore womans smile, regenerating bone to hold dental implants

Durham, NC (PRWEB) November 05, 2014

Half of all traumatic injuries to the face result in a loss of teeth and the surrounding tissue and bone that once supported them, which in turn makes these types of injuries very debilitating and difficult to treat. But in a new study published in the latest issue of STEM CELLS Translational Medicine, doctors at the University of Michigan School of Dentistry (UMSoD), Ann Arbor, have found a new way to regenerate a patients jawbone through the use of stem cells.

The procedure, done under local anesthesia, significantly speeds up the healing time relative to that of traditional bone grafting while allowing a patient to experience only a minimal amount of pain.

Part of a larger clinical trial, the findings highlighted in this issue focus on a 45-year-old woman missing seven front teeth plus 75 percent of the bone that once supported them, the result of a blow to her face five years earlier. She was left with severe functional and cosmetic deficiencies, since the missing bone made it impossible for her to have dental implant-based teeth replacements.

Darnell Kaigler, DDS, MS, PhD, an assistant professor of dentistry in the Department of Periodontics and Oral Medicine, was a lead member of the study team. "In small jawbone defects of the mouth created after teeth were extracted, we have placed gelatin sponges populated with stem cells into these areas to successfully grow bone."

Since the sponge material is soft, it does not work in larger areas. Thus, he and his team of researchers decided to try b-tricalcium phosphate (b-TCP) as a scaffold upon which to place the cells instead. "For treating larger jawbone defects, it is important to have a scaffold material that is rigid and more stable to support bone growth," he explained.

They then placed the b-TCP scaffold, which had been seeded with a mixed population of bone marrow-derived autologous stem and progenitor cells 30 minutes prior to treatment at room temperature, into the defective area of the patients mouth during a procedure that requires only local anesthesia. Four months later, 80 percent of her missing jawbone had been regenerated, allowing them to proceed with placing oral implants that supported a dental prosthesis to once again give her a complete set of teeth.

Study team member Sharon Aronovich, DMD, FRCD(C), a clinical assistant professor of dentistry in the Department of Oral and Maxillofacial Surgery at the UMSoD, said, I am very grateful to all the patients and researchers that participated in this study. Thanks to everyone's efforts, we are one step closer to providing patients with a minimally invasive option for implant-based tooth replacement.

As the first report to describe a cell therapy for craniofacial trauma reconstruction, this research serves as the foundation for expanded studies using this approach, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Stem cells help doctors restore womans smile, regenerating bone to hold dental implants

Ladera Ranch teen trying new strategies in her miraculous cancer fight

After four surgeries, six kinds of chemotherapy, stem cell transplants, 12 radiation treatments and antibody treatments, Katie Hawley beat cancer. Twice.

Katie, then 9, learned she had cancer in 2009, when doctors found an-egg sized, stage 3 tumor in her stomach, the cause of her pain and nausea. The rare tumor strikes fewer than five out of every 1 million children each year, according to the National Institute of Health.

In my heart, I hoped and believed she would beat this and live to 100, said Mary Kay Hawley, Katies mom. Yet, that quiet voice would whisper the nightmarish words, She may not make it to her 10th birthday. With that I became her court jester I wanted to give her the world.

After she endured a yearlong battle with ganglio neuroblastoma, doctors found no evidence of cancer cells left in her body. For more than two years, the Ladera Ranch girl lived like a normal kid again aside from scans every three months.

Until the day before Valentines Day last year, when one of her routine CT scans showed the cancer had returned with a vengeance, spreading to her skull, hips and legs.

I was terrified that I was going to lose her, Hawley said. She fell to her knees and begged God to spare her daughter. I prayed until I had peace.

Katie, now a freshman at San Juan Hills High, was sent to undergo an experimental, strong chemotherapy treatment in San Francisco. She had a 33 percent chance of improvement, 33 percent chance the disease would stay the same and 33 percent chance it would get worse. There was a 1 percent chance the treatment would kill the cancer cells, Hawley said.

Katie turned out to be the 1 percent and had a scan clear of cancer in June last year.

KEEPING THE CANCER AT BAY

To stop the cancer from returning, Katie was put on an aggressive, 10-month, in-home chemotherapy with Accutane treatments, making her extremely sick, tired and depressed, Hawley said. She took 14 pills a day, went to the hospital twice a week for blood tests and checkups and continued with CT scans every three months to check that the cancer hadnt returned.

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Ladera Ranch teen trying new strategies in her miraculous cancer fight

SPOTTING CANCER IN STEM CELLS

By Bradley J. Fikes U-T5:07 a.m.Nov. 5, 2014

A small fraction of cancer cells is responsible for spreading tumors to distant points of the body, according to a growing amount of scientific evidence. These cells, often called cancer stem cells, have become the target of intense research in recent years.

Most cancer cells dont appear to have the property of metastasis. They just stay in the tumor. And while primary tumors cause problems, oncologists said metastatic tumors are the real killers. They can lodge in critical places such as the lung, liver and brain.

Failure to eliminate cancer stem cells during treatment may be a big reason why many cancers return after remission. If so, then all those cells must be destroyed, with as little damage as possible to normal cells. Detecting and genetically analyzing cancer stem cells could provide clues to more-effective treatments.

After Jeff Allens wife died of cancer in 2012, the analytical biochemist put his training to work in learning more about the disease.

Doing so was initially a hobby, he said. As time progressed, it became more than a hobby. It became a downright obsession. I got angry at cancer, and as the years went by, I became frustrated with the slow pace of new weapons against it.

Allen, whose background includes development of molecular diagnostic devices, began studying how cancer treatment could be improved.

Now he and his sons, Alexander and Austin, said theyve designed a device that can detect the most dangerous cancer cells, often called cancer stem cells. The device is still in the concept phase, but local scientists who have looked at the technology think its feasible.

The device is envisioned as a microchip that examines a patients blood sample to identify and isolate cancer stem cells. Once captured, these cells would be genetically sequenced to find the mutations driving the cancer. Then doctors could prescribe the most customized treatment based on this more rigorous analysis.

To carry out his plan, Allen is seeking $50,000 through the crowdfunding site gofundme.com, at gofundme.com/7mznuo. He also has formed a company, TumorGen MDx.

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SPOTTING CANCER IN STEM CELLS

Global Stem Cells Group to Hold Practical, Hands-on Training Course on Adipose-derived Stem Cell Harvesting, Isolation …

Miami, FL (PRWEB) November 05, 2014

Global Stem Cells Group, its subsidiary Stem Cell Training, Inc. and Dr. J. Victor Garcia have announced plans to conduct the Adipose Derived Harvesting, Isolation and Re-integration Training Course in Barcelona, Spain Nov. 22-23. 2014.

The two-day, hands-on intensive training course, which will be conducted by Garcia, was developed for physicians and high-level practitioners to learn techniques in harvesting and reintegrating stem cells derived from adipose tissue and bone marrow. The objective of the training is to bridge the gap between bench science in the laboratory and the doctors office by teaching effective, in-office regenerative medicine techniques.

For more information, visit the Stem Cell Training, Inc. website, email info(at)stemcelltraining(dot)net, or call 305-224-1858.

About Global Stem Cells Group:

Global Stem Cells Group, Inc. is the parent company of six wholly owned operating companies dedicated entirely to stem cell research, training, products and solutions. Founded in 2012, the company combines dedicated researchers, physician and patient educators and solution providers with the shared goal of meeting the growing worldwide need for leading edge stem cell treatments and solutions.

With a singular focus on this exciting new area of medical research, Global Stem Cells Group and its subsidiaries are uniquely positioned to become global leaders in cellular medicine.

Global Stem Cells Groups corporate mission is to make the promise of stem cell medicine a reality for patients around the world. With each of GSCGs six operating companies focused on a separate research-based mission, the result is a global network of state-of-the-art stem cell treatments.

About Stem Cell Training, Inc.:

Stem Cell Training, Inc. is a multi-disciplinary company offering coursework and training in 35 cities worldwide. Coursework offered focuses on minimally invasive techniques for harvesting stem cells from adipose tissue, bone marrow and platelet-rich plasma. By equipping physicians with these techniques, the goal is to enable them to return to their practices, better able to apply these techniques in patient treatments.

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Global Stem Cells Group to Hold Practical, Hands-on Training Course on Adipose-derived Stem Cell Harvesting, Isolation ...

Okyanos Treats First Patients with Cell Therapy

Freeport, Grand Bahama (PRWEB) November 05, 2014

Okyanos is the first to receive regulatory approval from the National Stem Cell Ethics Committee (NSEC) to provide adult stem cell therapy in its new state-of-the-art facility and has now begun treating patients. The licensing includes approval for cardiac cell therapy, as well as cell therapy for tissue ischemia, autoimmune diseases, and other chronic neurological and orthopedic conditions. The licensing criteria requires that approved protocols be supported by peer-reviewed papers showing substantial evidence of safety and efficacy.

"As the leader in cell therapy, Okyanos is very proud to bring a new standard of care and a better quality of life to patients who are looking for new options for unmet healthcare needs. said Matt Feshbach, CEO and co-founder of Okyanos. Adipose (fat)- derived stem and regenerative cells (ADRCs) are known to restore blood flow, modulate the immune system, reduce inflammation and prevent further cell death after a wound, helping the body begin the process of healing itself.

Adult stem cell therapy has emerged as a new treatment alternative for those who want to live a more normal life but are restricted in these activities due to their medical conditions. Just 50 miles from the US shore, Okyanos cell therapy is available to patients with severe heart disease including coronary artery disease (CAD) and congestive heart failure (CHF) as well as patients with auto-immune diseases, orthopedic, neurological and urological conditions. Okyanos cell therapy is performed in their new state-of-the-art facility built to exceed U.S. surgical center standards.

With the regulatory and licensing approvals for adult stem cell therapy, Okyanos is the first to treat patients with cell therapy for severe heart disease and other unmet medical conditions based on a combination of internationally approved cell processing technology, technical papers, clinical trials and in-clinic use which provide the basis for a new standard of care.

Patients can contact Okyanos at http://www.okyanos.com or by calling toll free at 1-855-659-2667.

About Okyanos: (Oh key AH nos) Based in Freeport, Grand Bahama, Okyanos brings a new standard of care and a better quality of life to patients with coronary artery disease, tissue ischemia, autoimmune diseases, and other chronic neurological and orthopedic conditions. Okyanos Cell Therapy utilizes a unique blend of stem and regenerative cells derived from patients own adipose (fat) tissue which helps improve blood flow, moderate destructive immune response and prevent further cell death. Okyanos is fully licensed under the Bahamas Stem Cell Therapy and Research Act and adheres to U.S. surgical center standards. The literary name Okyanos, the Greek god of the river Okyanos, symbolizes restoration of blood flow.

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Okyanos Treats First Patients with Cell Therapy

Hunting for cancer stem cells

Jeff Allen, who is developing a cancer diagnostic chip similar to this one, poses for a picture in Nick Cosford's research lab at the Sanford Burnham Medical Research Institute. The chip Allen is developing would isolate cancer stem cells for diagnosis.

After Jeff Allens wife died of cancer in 2012, the analytical biochemist put his training to work in learning more about the disease.

Doing so was initially a hobby, he said. As time progressed, it became more than a hobby. It became a downright obsession. I got angry at cancer, and as the years went, by I became frustrated with the slow pace of developing new weapons against it.

Allen, whose background includes development of molecular diagnostic devices, began studying how cancer treatment could be improved.

Now he and his sons, Alexander and Austin, said theyve designed a device that can detect the most dangerous cancer cells, often called cancer stem cells. The device is still in the concept phase, but scientists who have looked at the technology think its feasible.

The device is envisioned as a microchip that examines a patients blood sample to identify and isolate cancer stem cells. Once captured, these cells would be genetically sequenced to find the mutations driving the cancer. Then doctors could prescribe the most customized treatment based on this more rigorous analysis.

To carry out his plan, Allen is seeking $50,000 through the crowdfunding site gofundme.com. He also has formed a company, TumorGen MDx.

In the world of oncology, theres increasing but not total recognition of cancer stem cells and their destructive role. Allen said his own reading of the literature is that these cells do indeed exist. They possess distinct characteristics that enable them to seed an entire new tumor from just a few cells, or perhaps only one.

That theory carries tremendous significance for accurate diagnosis. A drug that inhibits most cancer cells but misses the cancer stem cells wont do much good.

Jeff Allen's video promoting his work for a test to detect cancer stem cells.

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Hunting for cancer stem cells