The research involved creating human cells in a laboratory dish instead of relying on tests on mice. Photograph: corfield / Alamy/Alamy

Cells used to study dementia in a dish have led scientists to a potential new treatment strategy for an inherited form of the brain disease.

Defective stem cells grown in the lab revealed a signalling pathway linked to frontotemporal dementia (FTD), which accounts for about half of dementia cases before the age of 60.

Treatment with a drug that suppressed the pathway, known as Wnt, restored the ability of neurons affected by the disease to develop normally.

Prof Philip Van Damme, from the Leuven Research Institute for Neuroscience and Disease in Belgium, said: Our findings suggest that signalling events required for neurodevelopment may also play major roles in neurodegeneration.

Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia.

Mutations in the progranulin (GRN) gene are commonly associated with FTD, which results in damage to the frontal and temporal lobes of the brain.

The fact that GRN mutations produced in mice do not display all the features of the human disorder has limited progress towards effective treatments for FTD.

Instead of relying on animal tests, the new research involved creating human cells in a laboratory dish.

The scientists reprogrammed skin cells from three dementia patients into induced pluripotent stem cells (iPSCs), immature cells that mimic stem cells taken from early-stage embryos.

Original post:
Stem cell study leads to potential new dementia treatment

IMAGE:Induced pluripotent stem cells (iPSCs) derived from patients with frontotemporal dementia were genetically corrected and converted to cortical neurons. The green staining indicates the cortical marker CTIP2, the red stain... view more

Credit: Susanna Raitano/Stem Cell Reports 2014

Belgian researchers have identified a new strategy for treating an inherited form of dementia after attempting to turn stem cells derived from patients into the neurons most affected by the disease. In patient-derived stem cells carrying a mutation predisposing them to frontotemporal dementia, which accounts for about half of dementia cases before the age of 60, the scientists found a targetable defect that prevents normal neurodevelopment. These stem cells partially return to normal when the defect is corrected.

The study appears in the December 31st issue of Stem Cell Reports, the official journal of the International Society of Stem Cell Research published by Cell Press.

"Use of induced pluripotent stem cell (iPSC) technology"--which involves taking skin cells from patients and reprogramming them into embryonic-like stem cells capable of turning into other specific cell types relevant for studying a particular disease--"makes it possible to model dementias that affect people later in life," says senior study author Catherine Verfaillie of KU Leuven.

Frontotemporal disorders are the result of damage to neurons in parts of the brain called the frontal and temporal lobes, gradually leading to behavioral symptoms or language and emotional disorders. Mutations in a gene called progranulin (GRN) are commonly associated with frontotemporal dementia, but GRN mutations in mice do not mimic all the features of the human disorder, which has limited progress in the development of effective treatments.

"iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons," Verfaillie says.

Verfaillie and Philip Van Damme of the Leuven Research Institute for Neuroscience and Disease explore this approach in the Stem Cell Reports study by creating iPSCs from three patients carrying a GRN mutation. These immature cells were impaired at turning into mature, specialized cells called cortical neurons--the most affected cell type in frontotemporal dementia.

One of the top defective pathways in the iPSCs was the Wnt signaling pathway, which plays an important role in neuronal development. However, genetic correction or treatment with a compound that inhibits the Wnt signaling pathway restored the ability of the iPSCs to turn into cortical neurons. Taken together, the findings demonstrate that the GRN mutation causes the defect in cortical neuron formation by altering the Wnt signaling pathway.

"Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration," Van Damme says. "Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia."

Continued here:
Patient stem cells used to make dementia-in-a-dish; help identify new treatment strategy

NEW YORK (TheStreet) -- Shares of stem cell therapy developerNeuralstem (CUR) rose 4.62% to $2.72 on higher-than-average volume in afternoon trading Wednesday in sympathy with peer companyBrainstorm Cell Therapeutics (BCLI) .

Brainstorm intends to release the final results from its Phase 2a trial of its stem cell therapy NurOwn on Monday. The company describes NurOwn as an "autologous, adult stem cell therapy technology" designed to treat ALS, also known as Lou Gehrig's Disease.

The company will host a conference call on Monday to discuss the results.

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One Reason Neuralstem (CUR) Stock is Rising Today

NEW YORK (TheStreet) -- Shares ofBrainstorm Cell Therapeutics (BCLI) soared 20.88% to $4.69 on higher-than-average volume in morning trading Wednesday ahead of the biotech company's data release on Monday.

Brainstorm intends to release the final results from its Phase 2a trial of its stem cell therapy NurOwn on Monday. The company describes NurOwn as an "autologous, adult stem cell therapy technology" designed to treat ALS, also known as Lou Gehrig's Disease.

The company will host a conference call on Monday to discuss the results.

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Jim Cramer and Stephanie Link reveal their investment tactics while giving advanced notice before every trade.

Access the tool that DOMINATES the Russell 2000 and the S&P 500.

Jim Cramer's protg, David Peltier, uncovers low dollar stocks with extraordinary upside potential that are flying under Wall Street's radar.

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Brainstorm Cell Therapeutics (BCLI) Stock Rises Ahead of ALS Treatment Trial Data Release

Washington, DC - infoZine - Three-year outcomes from an ongoing clinical trial suggest that high-dose immunosuppressive therapy followed by transplantation of a person's own blood-forming stem cells may induce sustained remission in some people with relapsing-remitting multiple sclerosis (RRMS). RRMS is the most common form of MS, a progressive autoimmune disease in which the immune system attacks the brain and spinal cord.

Three years after the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant or HDIT/HCT, nearly 80 percent of trial participants had survived without experiencing an increase in disability, a relapse of MS symptoms or new brain lesions. Investigators observed few serious early complications or unexpected side effects, although many participants experienced expected side effects of high-dose immunosuppression, including infections and gastrointestinal problems.

Scientists estimate that MS affects more than 2.3 million people worldwide. Symptoms can vary widely and may include disturbances in speech, vision and movement. Most people with MS are diagnosed with RRMS, which is characterized by periods of relapse or flare up of symptoms followed by periods of recovery or remission. Over years, the disease can worsen and shift to a more progressive form.

In the study, researchers tested the effectiveness of HDIT/HCT in 25 volunteers with RRMS who had relapsed and experienced worsened neurological disability while taking standard medications. Doctors collected blood-forming stem cells from participants and then gave them high-dose chemotherapy to destroy their immune systems. The doctors returned the stem cells to the participants to rebuild and reset their immune systems.

"Notably, participants did not receive any MS drugs after transplant, yet most remained in remission after three years," said Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology and Transplantation. "In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects."

The study researchers plan to follow participants for a total of five years, recording all side effects associated with the treatment. Final results from this and similar studies promise to help inform the design of larger trials to further evaluate HDIT/HCT in people with MS.

The trial is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network (ITN).

The three-year findings are published in the Dec. 29, 2014, online issue of JAMA Neurology.

Related Link Immune Tolerance Network (ITN)

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Stopping Multiple Sclerosis with Stem Cell Transplants

Anyone can be a bone marrow donor, but when it comes to finding a match, race can be everything. There are certain genetic markers that doctors will look for when searching for a match -- and if a match is made, a transplant can then be scheduled. If someone is in need of a transplant, the process can be daunting, especially if there is only a small pool of donors that share a similar ethnicity.

There are many bone marrow donor services throughout the country, but the Asian American Donor Program (AADP) is a champion nonprofit dedicated to increasing the availability of potential stem cells donors for patients with life threatening diseases curable by a stem cell transplant. Based in Alameda, CA, AADP holds donor registration drives and outreach events to Asian, Pacific Islander, and mixed race communities in the Bay Area.

Stem cells are found inside bone marrow, and those cells can turn into red blood cells, white blood cells and platelets. AADP explains that red blood cells carry oxygen throughout the body; white blood cells help fight infections; and platelets help control bleeding. Diseases like leukemia, sickle cell anemia, blood cancers, and many other immune diseases can be treated with a bone marrow or stem cell transplant. This soft tissue is incredibly important to our health.

To learn more about why bone marrow donation is important, and why it is particularly important in Asian Pacific American and mixed race communities, I reached out to Ruby Law, AADP's Recruitment Director.

Hyphen: When does one need a bone marrow donation, and what does it do?

Ruby Law: Disease can affect the marrows ability to function. When this happens, a bone marrow or cord blood transplant could be the best treatment option. For some diseases, transplant offers the only potential cure. A bone marrow or cord blood transplant replaces unhealthy blood-forming cells with healthy ones. Blood-forming cells are also called blood stem cells. Blood stem cells are immature cells that can grow into red blood cells, white blood cells and platelets. Every year, 12,000 patients with blood diseases such as leukemia and lymphoma, sickle cell and other life-threatening diseases need a bone marrow or umbilical cord blood transplant.

Hyphen: Why is bone marrow donation important for Asian Pacific American and mixed-Asian Pacific Americans communities to address in discussions about health?

RL: A patient needs a matching donor for a successful transplant. The closer the match, the better for the patient. Patients are more likely to match someone from their own race or ethnicity. For example a Chinese patient will most likely need a Chinese donor, while a Japanese patient will most likely need a Japanese donor. Out of 10 million registrants in the United States, only 7% of the registrants are Asian and only 4% are of mixed race. Most Asian or Mixed Asian patients cannot find any matching donor in the registry because there are not enough Asian, mixed Asian and minority donors.

Ruby Law, Asian American Donor Program (AADP) Recruitment Director

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Down to the Bone: The Need for API Bone Marrow Donors

KINDHEARTED Andrew Gibson is giving somebody the gift of life, after being inspired by a workmates little boy.

Andrew, 29, from Southend, signed up to the bone marrow transplant register after hearing about 21-month-old Jack Kleinberg.

Jack, of St James Gardens, Westcliff, is facing the second bone marrow transplant in his short life to help him beat two life-threatening conditions.

His parents are hoping the op will fight the effects of Wiskott Aldrich syndrome and familial Mediterranean fever.

After hearing Jacks story, from Jacks mum, Vicki Parrott, a workmate at the Hood Groups Southend insurance office, Andrew donated stem cells for use by an un-named patient in need.

Andrew was disappointed to learn he wouldnt be a match for Jack, but decided to go ahead all the same and Ms Parrott is delighted her son's example is helping others in need.

She said: At the office Christmas party, I found out Andrew, who had joined the Anthony Nolan bone marrow register when Jack first got ill, was recently called up as a match. He donated his stem cells a month ago to a stranger.

I couldn't believe it. I was so emotional and hugged him loads. I dont know if well ever meet Jacks donor, so this is the closest thing weve had.

Its overwhelming to think theres someone out there whos had a second chance at life because of Jacks story. Itsmade my year.

Andrew said: There was an email going around at work, urging people to sign up to the Anthony Nolan register, as a way of showing our support for Vicki and her son Jack, who had just been diagnosed. Id never heard of Anthony Nolan before, but I didnt hesitate. Seeing Vicki at the Christmas party really made it sink in what Id done. It was an emotional moment and it was clear how much it meant to her.

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Andrew donates bone marrow after hearing about brave boy

NIH-funded study yields encouraging early results

Three-year outcomes from an ongoing clinical trial suggest that high-dose immunosuppressive therapy followed by transplantation of a person's own blood-forming stem cells may induce sustained remission in some people with relapsing-remitting multiple sclerosis (RRMS). RRMS is the most common form of MS, a progressive autoimmune disease in which the immune system attacks the brain and spinal cord. The trial is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network (ITN) .

Three years after the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant or HDIT/HCT, nearly 80 percent of trial participants had survived without experiencing an increase in disability, a relapse of MS symptoms or new brain lesions. Investigators observed few serious early complications or unexpected side effects, although many participants experienced expected side effects of high-dose immunosuppression, including infections and gastrointestinal problems. The three-year findings are published in the Dec. 29, 2014, online issue of JAMA Neurology.

These promising results support the need for future studies to further evaluate the benefits and risks of HDIT/HCT and directly compare this treatment strategy to current MS therapies, said NIAID Director Anthony S. Fauci, M.D. If the findings from this study are confirmed, HDIT/HCT may become a potential therapeutic option for people with this often-debilitating disease, particularly those who have not been helped by standard treatments.

Scientists estimate that MS affects more than 2.3 million people worldwide. Symptoms can vary widely and may include disturbances in speech, vision and movement. Most people with MS are diagnosed with RRMS, which is characterized by periods of relapse or flare up of symptoms followed by periods of recovery or remission. Over years, the disease can worsen and shift to a more progressive form.

In the study, researchers tested the effectiveness of HDIT/HCT in 25 volunteers with RRMS who had relapsed and experienced worsened neurological disability while taking standard medications. Doctors collected blood-forming stem cells from participants and then gave them high-dose chemotherapy to destroy their immune systems. The doctors returned the stem cells to the participants to rebuild and reset their immune systems.

Notably, participants did not receive any MS drugs after transplant, yet most remained in remission after three years, said Daniel Rotrosen, M.D., director of NIAIDs Division of Allergy, Immunology and Transplantation. In contrast, other studies have shown that the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects.

The study researchers plan to follow participants for a total of five years, recording all side effects associated with the treatment. Final results from this and similar studies promise to help inform the design of larger trials to further evaluate HDIT/HCT in people with MS.

The work was sponsored by NIAID, NIH, and conducted by the ITN (contract number N01 AI015416) and NIAID-funded statistical and clinical coordinating centers (contract numbers HHSN272200800029C and HHSN272200900057C). The ClinicalTrials.gov identifier for the study High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is NCT00288626.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

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News & Events

NEW DELHI: India may soon have an official database on stem cell donors and recipients. The health ministry is evaluating a proposal along with All India Institute of Medical Sciences (AIIMS) to create a donor registry as part of the National Health Mission (NHM), a senior official told TOI.

The proposal suggests enrolling all district hospitals in the first phase to seek stem cell details from across the country. "Once a stem cell donor registry is in place, a willing donor can be contacted and one can coordinate easily. Also, this would enhance access to safe blood," the official said.

Stem cells, found in bone marrow, are like building blocks which can grow into any normal cell of the body such as red blood cells to carry oxygen, white blood cells to fight infection, or platelets to stop bleeding.

Apart from the donor registry, the ministry is also looking at creating facilities for human leucocyte antigen (HLA) typing. HLA-typing is a process conducted for matching donors and recipients of stem cell. HLA-typing is necessary to minimize rejection of stem cell transplant, experts say.

Once created, this would be the first government registry in the country. Till now, such registries have been run in the country by a few NGOs such as Bharat Stem Cells.

According to Bharat Stem Cells, there is usually 25% chance of a patient finding a matching donor within the family. The rest depend on unrelated voluntary stem cell donors.

Stem cell therapy has been shown to be effective in various blood disorders and in treatment of cancer. It is widely used in bone marrow transplantation. However, stem cell treatment remains expensive because of limited research as well as unavailability and lack of coordination between donors and recipients. Some private hospitals charge as much as Rs 1 lakh per session for stem cell therapy. On an average, stem cell treatment is estimated to cost around Rs 15-16 lakh.

According to the official, the idea behind including stem cell into NHM is to make it affordable by creating records and providing facilities.

Stay updated on the go with The Times of Indias mobile apps. Click here to download it for your device.

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Stem cell registry will make cancer treatment cheaper

John and Leslie Malone pose with Maikel at Harmony Sporthorses, December 2, 2014.

The largest ever cash donation to Colorado State University stems from a novel treatment to get a dressage horse with a bum knee back into the show ring.

John and Leslie Malone's $42.5 million gift, announced Monday, will create the CSU Institute for Biologic Translational Therapies in the College of Veterinary Medicine and Biomedical Sciences, a 100,000-square-foot facility to develop stem-cell research into commercially viable treatments for animals and humans.

"This is the largest cash gift in the history of the university and it's absolutely staggering," said Brett Anderson, CSU's vice president for advancement. "It really allows us to be the best in the nation."

The Malone money will fund half of the $65 million cost to construct the facility. The school is looking for more donations to match the Malones' contribution. So far, an additional $10 million has been raised.

The Malones also provided $10 million to cover the Institute's operating expenses once the facility is built.

"The Malones have been so gracious. We asked them if they want to put their name on the building, but they said if it's helpful to you in order to get another major donor, we are happy to let you name it for someone else," Anderson said. "They are an incredible couple."

John Malone, who made his millions at the helm of Tele-Communications Inc. and now chairs the giant Liberty Media Corp., and his wife, Leslie, could not be reached for comment on Monday.

The Malones, who raise and train dressage and jumping horses on a ranch near Kiowa, last year donated $6 million to the school to establish the Leslie A. Malone Presidential Chair in Equine Sports Medicine.

They later brought Blixt, their dressage horse with a bad knee, to the vet school's Orthopaedic Research Center.

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Malones donate $42.5 million to CSU for new stem-cell research facility

Scientists are now creating primordial germ cells (precursors to egg and sperm) with human stem cells and even skin cells. This new work,published inCelltoday, takes us beyond what was previously just done using stem cells.

One of the first events in the early development of both mice and men is the creation of primordial germ cells (PGCs). After an egg is fertilized by sperm, embryonic stem cells begin to differentiate into various basic cell types that make up the fetus. A small number of these stem cellsdevelop into primordial germ cells, which will go on to become egg or sperm. Germ cells are immortal in the sense that they provide an enduring link between all generations, carrying genetic information from one generation to the next,Cambridges Azim Suranisays in auniversity statement.

Researchers have now figured out how to reprogram cells to act like embryonic stem cells. These induced pluripotent stem (iPS) cells have been used to develop humanretinasandintestines, for example, according to IFLScience. Researchers have also created iPS cells that could differentiate into primordial germ cells, but its only been successful in rodents.

Now, a team of researchers from the U.K. and Israel traced the genetic chain of events that directs a human stem cell to develop into a primordial germ cell. This stage in our development is called specification,and once PGCs become specified,they continue developing toward precursor sperm cells or ova pretty much on autopilot,Jacob Hanna from the Weizmann Institute of Sciencesays in anews release.

A master gene called SOX17 works to direct stem cells which in previous studies was found to direct stem cells into becoming lung, gut and pancreas cells. But the gene working as part of primordial germ cell specification is a new development.

The international team followed their discovery by actually making primordial germ cells in the lab. Using both embryonic stem cells and iPS cells (reprogrammed adult skin cells) from both males and females, the researchersmade sex cell precursors with up to 40 percent efficiency. When they compared the protein markers of their new, lab-grown PGCs with real PGCs collected from aborted fetuses,Nature reports, they were found to be very similar.

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Skin cells are being used to create artificial sperm and eggs

A UCSF spinout is growing neuronal stemcells to transplant into the brain, for potential use in treating epilepsy, spinal cord injury, Parkinsons and Alzheimers disease and investors are listening. Because one thing thatdifferentiatesNeurona Therapeutics is that its stem cells turn exclusively intointerneuron cells which are less likely to be tumorigenic than other IPS cells.

The companyhasraised $7.6 million of a proposed $24.3 million round, according to a regulatory filing. But the companys staying a touch under the radar it lacks a website, and tis the season for calls to the company to remain unanswered.

But funding for the six-year-old company comes from 11 investors. Listed on the documents contact pages areTim Kutzkeyand David Goeddel, both partners at early stage healthcare venture firm The Column Group giving some insight into who the startupsinvestors are.

Also listed is Leo Guthart, a managing partner at New York private equity firm TopSpin Partner, and Arnold Kriegstein, director of the UCSF developmental and stem cell biology program.

Kriegsteinand his UCSF colleagues filed a patentfor the in vitro production of medial ganglionic eminence (MGE) precursor cells which are, in essence, immature cells that morphinto nerve cells. The work that led to the patent was funded bythe California Institute of Regenerative Medicine, the NIH and the Osher Foundation.

We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way,Kriegstein said in a UCSF statement last year.

Neurona Therapeutics scientific backers collaborated on a paper on these MGE cells inCell Stem Cell,finding that mouse models closely mimicked human cells inneural cell development and that human cells can successfully be transplanted into mouse brains. UCSF writes:

Kriegstein sees MGE cells as a potential treatment to better control nerve circuits that become overactive in certain neurological disorders. Unlike other neural stem cells that can form many cell types and that may potentially be less controllable as a consequence most MGE cells are restricted to producing a type of cell called an interneuron. Interneurons integrate into the brain and provide controlled inhibition to balance the activity of nerve circuits.

To generate MGE cells in the lab, the researchers reliably directed the differentiation of human pluripotent stem cells either human embryonic stem cells or induced pluripotent stem cells derived from human skin. These two kinds of stem cells have virtually unlimited potential to become any human cell type. When transplanted into a strain of mice that does not reject human tissue, the human MGE-like cells survived within the rodent forebrain, integrated into the brain by forming connections with rodent nerve cells, and matured into specialized subtypes of interneurons.

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Stem cells to transplant in the brain: Stealth UCSF spinout Neurona Therapeutics raises $7.6M

Abstract: Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.

Introduction

In the field of regenerative medicine, basic research and preclinical studies have been conducted to overcome clinical shortcomings with the use of mesenchymal stem cells (MSCs). MSCs are present in adult tissues, including bone marrow and adipose tissue. For many years, bone marrow-derived stem cells (BSCs) were the primary source of stem cells for tissue engineering applications (Caplan, 1991; Pittenger et al., 1999; Caplan, 2007). However, recent studies have shown that subcutaneous adipose tissue provides a clear advantage over other stem cell sources due to the ease with which adipose tissue can be accessed as well as the ease of isolating stem cells from harvested tissue (Schffler et al., 2007). Initial enzymatic digestion of adipose tissue yields a mixture of stromal and vascular cells referred to as the stromal-vascular fraction (SVF) (Traktuev et al., 2008). A putative stem cell population within this SVF was first identified by Zuk et al. and named processed lipoaspirate (PLA) cells (Zuk et al., 2001; Zuk et al., 2002).

There is no consensus when it comes to the nomenclature used to describe progenitor cells from adipose tissue-derived stroma, which can sometimes lead to confusion. The term PLA refers to adipose-derived stromal cells and adipose-derived stem cells (ASCs) and describes cells obtained immediately after collagenase digestion. Accordingly, the term ASC will be used throughout this review.

ASCs exhibit stable growth and proliferation kinetics and can differentiate toward osteogenic, chondrogenic, adipogenic, myogenic, or neurogenic lineages in vitro (Zuk et al., 2002; Izadpanah et al., 2006; Romanov et al., 2005). Furthermore, a group has recently described the isolation and culture of ASCs with multipotent differentiation capacity at the single-cell level (Rodriguez, et al., 2005).

Using these attractive cell populations, recent studies have explored the safety and efficacy of implanted/administrated ASCs in various animal models. Furthermore, clinical trials using ASCs have been initiated in some medical subspecialties. This review summarizes the current preclinical data and ongoing clinical trials and their outcomes in a variety of medical fields.

Characterization and Localization

ASCs express the mesenchymal stem cell markers CD10, CD13, CD29, CD34, CD44, CD54, CD71, CD90, CD105, CD106, CD117, and STRO-1. They are negative for the hematopoietic lineage markers CD45, CD14, CD16, CD56, CD61, CD62E, CD104, and CD106 and for the endothelial cell (EC) markers CD31, CD144, and von Willebrand factor (Zuk et al., 2002; Musina et al., 2005; Romanov et al., 2005). Morphologically, they are fibroblast-like and preserve their shape after expansion in vitro (Zuk et al., 2002; Arrigoni et al., 2009; Zannettino et al., 2008).

The similarities between ASCs and BSCs may indicate that ASCs are derived from circulating BSCs, which infiltrate into the adipose compartment through vessel walls (Zuk et al., 2002; Zannettino et al., 2008; Brighton et al., 1992; Canfield et al., 2000; Bianco et al., 2001). On the other hand, according to a recent theory, these stem cells are actually pericytes (Traktuev et al., 2008; Chen et al., 2009; Crisan et al., 2008; Zannettino et al., 2008; Tintut et al., 2003; Abedin et al., 2004; Amos et al., 2008). Pericytes around microvessels express alpha-smooth muscle actin (-SMA) as well as certain MSC markers (CD44, CD73, CD90, CD105); however, they do not express endothelial or hematopoietic cell markers (Chen et al., 2009). Pericytes adhere, proliferate in culture, sustain their initial antigenic profile, and can differentiate into bone, cartilage and fat cells (Chen et al., 2009). Moreover, injected MSCs migrate to the blood vessels in vivo and become pericytes (Chen et al., 2009). Considering the above-mentioned data, it can be speculated that pericytes are the ancestors of MSCs, but this does not mean that all MSCs are descendants of pericytes (Chen et al., 2009) or that all pericytes are necessarily stem cells (Lin et al., 2008; Traktuev et al., 2008; da Silva et al., 2008; Abedin et al., 2004; Tintut et al., 2003; Zannettino et al., 2008; Amos et al., 2008).

Traktuev et al. (2008) defined a periendothelial pericyte-like subpopulation of ASCs. These cells were CD34+, CD31-, CD45-, and CD144- and expressed mesenchymal cell markers, smooth muscle antigens, and pericytic markers, including chondroitin sulfate proteoglycan (NG2), CD140a, and CD140b (PDGF receptor and , respectively) (Traktuev et al., 2008; Amos et al., 2008). However, Lin et al. (2008) could not co-localize CD34 and CD104b, and thus concluded that CD34+/CD31- cells of adipose vasculature are not pericytes.

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Adipose-derived Stem Cells: Current Findings and Future ...

The body has evolved ways to get rid of faulty stem cells. A University of Colorado Cancer Center study published in the journal Stem Cells shows that one of these ways is a "program" that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. Radiation makes a stem cell lose its "stemness." That makes sense: you don't want damaged stem cells sticking around to crank out damaged cells.

The study also shows that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, we may be able to prevent cancer in the aftermath of full body radiation.

"The body didn't evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA," says James DeGregori, PhD, investigator at the CU Cancer Center, professor of Biochemistry and Molecular Genetics at the CU School of Medicine, and the paper's senior author.

DeGregori, doctoral student Courtney Fleenor, and colleagues explored the effects of full body radiation on the blood stem cells of mice. In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. Only, while most followed this instruction, a few did not. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their "stemness." Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it's not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation.

"It's about evolution driven by natural selection," DeGregori says. "In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. But when radiation reduces the heath and robustness (what we call 'fitness') of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over."

Think about it in terms of chipmunks and squirrels: reducing an ecosystem's population of chipmunks may allow squirrels to flourish -- especially if the way in which chipmunks are reduced changes the ecosystem to favor squirrels, similar to how radiation changes the body in a way that favors C/EBPA-mutant stem cells).

These studies don't just tell us why radiation makes hematopoietic stem cells (HSCs) differentiate; they also show that by activating a stem cell maintenance pathway, we can keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again -- restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.

When DeGregori, Fleenor and colleagues activated NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.

"If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs," DeGregori says, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their "programmed mediocrity" (increased differentiation) and even HSC with cancer-causing mutations. "But there's also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation."

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Reprogramming stem cells may prevent cancer after radiation

An experimental treatment that uses a patient's own stem cells may offer new hope for people with multiple sclerosis.

In a small clinical trial, patients experienced long-term disease remission after undergoing a transplant of their own hematopoietic stem cells. This type of cell is responsible for the formation of blood in the body and are typically derived from bone marrow. The patients also took high-dose immunosuppressive drugs.

The paper, published Monday in JAMA Neurology, reports on the third year of a five-year study. A total of 24 patients with active relapsing-remitting MS were enrolled in the trial. With this type of MS, patients have points when their disease is active followed by periods when they do not experience any symptoms.

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Dr. Jon LaPook goes inside the trial and approval process for an experimental treatment using stem cells designed to make Multiple Sclerosis pati...

The researchers found that nearly 79 percent of the patients who underwent the procedure sustained full neurologic function for the three years following the treatment and symptoms of their disease did not progress. Additionally, patients in that time period did not develop any new lesions related to their disease.

More than 90 percent of patients did not experience disease progression, while 86 percent did not have any periods of relapse. Though a small number of patients did have side effects from the immunosuppressive drugs, they were no different than the side effects typically experienced by MS patients taking the drugs who haven't undergone stem cell therapy.

"Longer follow-up is needed to determine the durability of the response," the authors write in the study. "Careful comparison of the results of this investigation and other ongoing studies will be needed to identify the best approaches for high-dose immunosuppressive therapies for MS and plan the next clinical studies."

The authors of an accompanying editorial say the research indicates this type of therapy has potential to work on patients who do not experience disease remission with medications alone, such as immunosuppressive drugs and anti-inflammatory drugs such as corticosteroids.

However, they add that "the jury is still out regarding the appropriateness and indication" of stem cell transplants for MS patients. Stem cell therapy is not approved by the U.S. Food and Drug Administration for the treatment of MS. The National Multiple Sclerosis Society currently funds 15 research projects on stem cell therapies that have the potential to prevent disease activity and repair nerve damage.

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Stem cell transplant may help patients with MS

Experimental treatment kills off, then 'resets' the immune system

WebMD News from HealthDay

By Dennis Thompson

HealthDay Reporter

MONDAY, Dec. 29, 2014 (HealthDay News) -- An experimental therapy that kills off and then "resets" the immune system has given three years of remission to a small group of multiple sclerosis patients, researchers say.

About eight in 10 patients given this treatment had no new adverse events after three years. And nine in 10 experienced no progression or relapse in their MS, said lead author Dr. Richard Nash of the Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center in Denver.

"I think we all think of this as a viable therapy," Nash said. "We still need to perform a randomized clinical trial, but we're all pretty impressed so far, in terms of what we've seen."

In multiple sclerosis, the body's immune system for some unknown reason attacks the nervous system, in particular targeting the insulating sheath that covers the nerve fibers, according to the U.S. National Institutes of Health. People with the more common form, called relapsing-remitting MS, have attacks of worsening neurologic function followed by partial or complete recovery periods (remissions).

Over time, as the damage mounts, patients become physically weak, have problems with coordination and balance, and suffer from thinking and memory problems.

This new therapy seeks to reset the immune system by killing it off using high-dose chemotherapy, then restarting it using the patient's own blood stem cells. Doctors harvest and preserve the patient's stem cells before treatment, and re-implant them following chemotherapy.

Read more:
Stem Cell Therapy for MS Shows Promise

Stem cells grown under low oxygen. These stem cells from Stemedica are licensed to CardioCell.

Dr. David Gorski, a prominent skeptic of therapies offered outside the scientifically controlled clinical trial system, has published an extensive and critical look at the stem cell therapy Gordie Howe received in early December to help him recover from a serious stroke.

I had email exchanges with Gorski while writing my article last week on the treatment, which uses stem cells provided by San Diego-based Stemedica. Gorski, whose previous blog post at Science-Based Medicine on Howe's treatment caught my attention, follows through with an analysis of the clinical trial setup used by Novastem, a Mexican stem cell company licensed by Stemedica to use its cells.

Dr. Murray Howe and his hockey great father, Gordie Howe, on a fishing trip in Saskatchewan in 2013. / Courtesy Murray Howe

"As sympathetic as I am to the Howe family, Im sorry. I reluctantly have to say that Murray Howe really should know better," Gorski wrote. "If Gordie Howe was treated as part of a clinical trial, then Novastem should have treated him for free! Thats because if it is running a clinical trial, it should treat everyone on the trial for free. Thats the way its done ethically."

I asked Novastem president Rafael Carrillo about the financial issue for my article. Carrillo said Novastem doesn't have deep pockets like a big pharmaceutical company, so it needs to charge for the treatment to pay its expenses. Without that money, it can't afford the trial. Patients wouldn't get the opportunity to get care that could help them, Carrillo said. Moreover, this arrangement is legal under Mexican law.

Gorksi views this as unethical, even if it's legal. He objects to the free treatment given to Gordie Howe, because it amounts to publicity for Novastem that will attract paying customers. And even if Howe is doing better, as appears to be the case, it's not possible to tell definitively whether stem cells helped.

The U.S. system has its own flaws, Gorski says, because patient expenses not related to the clinical trial are not paid for.

"Patients who dont have health insurance will often have a huge difficulty paying for their care not related to the clinical trial and thus will have difficulties accessing cutting-edge clinical trials because they cant pay for their own regular care," Gorski wrote. "Yay, USA!"

Stemedica is offering its own U.S. trial of the therapy, but people must have had the stroke at least six months ago. That's because people make the most improvement within six months after a stroke. So delaying treatment until after that point will make it easier to detect improvement caused by the stem cell treatment.

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More about Gordie Howe's therapy

Spinal cord injuries are devastating, leaving the person injured facing a life time of challenges, and placing a huge strain on their family and loved ones who help care for them.

The numbers affected are not small. More than a quarter of a million Americans are living with spinal cord injuries and there are more than 11,000 new cases each year.

Its not just a devastating injury, its also an expensive one. According to the National Spinal Cord Injury Statistical Center it can cost more than $775,000 to care for a patient in the first year after injury, and the estimated lifetime costs due to spinal cord injury can be as high as $3 million.

Right now there is no cure, and treatment options are very limited. We have heard for several years now about stem cell research aimed at helping people with spinal cord injuries, but where is that research and how close are we to testing the most promising approaches in people?

Thats going to be the focus of a Google Hangout on Spinal Cord Injury and Stem Cell Research that we are hosting tomorrow, Tuesday, November 18 from noon till 1pm PST.

Well be looking at the latest stem cell-based treatments for spinal cord injury including work being done by Asterias Biotherapeutics, which was recently given approval by the Food and Drug Administration (FDA) to start a clinical trial for spinal cord injury. We are giving Asterias $14.3 million to carry out that trial and you can read more about that work here.

Were fortunate in having three great guests for the Hangout: Jane Lebkowski, Ph.D., the President of research and development at Asterias; Roman Reed, a patient advocate and tireless champion of stem cell research and the founder of the Roman Reed Foundation; and Kevin Whittlesey, Ph.D., a CIRM science officer, who will discuss other CIRM-funded research that aims to better understand spinal cord injury and to bring stem cell-based therapies to clinic trials.

You can find out how to join the Hangout by clicking on the event page link: http://bit.ly/1sh1Dsm

The event is free and interactive, so youll be able to ask questions of our experts. You dont need a Google+ account to watch the Hangout just visit the event page at the specified time. If you do have a G+ account, please RSVP at the event page (link shown above). Also, with the G+ account you can ask questions in the comment box on this event page. Otherwise, you can tweet questions using #AskCIRMSCI or email us at info@cirm.ca.gov.

We look forward to seeing you there!

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Spinal cord injury and stem cell research; find out the ...

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun. Reminding broken hearts how to mend them selves. After years of tracking down the right genetic buttons a team at the Salk Institute in La Jolla has taught a mammal to do what zebra fish do naturally, repair a severely damaged heart. While all our cells have the genetic code for building whole organs those genes seem to be switched off in all higher animals, but active in some more primitive species like zebra fish and salamanders.

New cells (red) repairing injury in a zebra fish heart.

When, with CIRM funding, they inserted genetic signals to turn off those genes in the mice, they saw significant repair of the damaged heart. There are many steps between this advance and getting human hearts to repair them selvesnotably finding a way to introduce the genetic signals without using the virus used in this study. HealthCanal picked up the institutes press release.

Cloned stem cells pretty much like reprogrammed stem cells. In the early days of stem cell research there was a great deal of excitement about the possibility of creating stem cells that genetically match a patient by a process commonly called cloning. This process of taking the genetic storehouse of a cell, the nucleus, and inserting it into a donor egg had been relatively easy in mice. But it turned out quite difficult in humans and was only accomplished last year.

During the years of failed attempts at this process known as nuclear transfer in humans an alternative came into the field. The Nobel prize-winning discovery that you can reprogram any adult cell to act like an embryonic stem cell gave us a new way to create personalized stem cells that genetically match a patient. But ever since that 2008 advance, the research community has fretted over whether those new stem cells called iPS cells really match embryonic stem cells. The iPS cells came from older cells that had lived through many opportunities for mutation and the genetic factors used to reprogram them added further opportunities for mutation.

Researchers at the New York Stem Cell Foundations in house lab have now compared the two types of cells with several layers of genetic analysis. They found the same level of mutation in the iPS cells and the cells from nuclear transfer lending some reassurance to the use of iPS cells going forward. HealthCanal ran the foundations press release.

A more efficient way to make cloned stem cells. Even though a team in Oregon overcame the obstacles to creating stem cells by nuclear transfer last year, and the feat has been repeated by the New York team above and others, it remains terribly inefficient. So, several groups are working on better ways to make these potentially valuable cells.

A former colleague now at Childrens Hospital, Boston wrote a nice explanation of how researchers are going about making these cloned cells easier in the hospitals blog, Vector. Stem cells reduced seizures. The seizures endured by people with many forms of epilepsy originate from genetic defects in their nerves. So, a team at McClean Hospital outside of Boston implanted healthy nerves grown from embryonic stem cells in mice with genetically linked seizures. Half the mice no longer had seizures and the other half had their seizure frequency reduced.

The type of nerves transplanted are called interneurons, which are known to be the nerves that reduce firing of signals. In epilepsy nerve signals are hyperactive. The team is now working on methods to mature the stem cells into purer populations of just the desired interneurons. ClinicalSpace picked up the hospitals press release.

Don Gibbons

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Stem cell stories that caught our eye: heart repair ...

First it was stem cells from rare apples touted as a revolution in anti-aging skin care. Then every other plant (seller) decided to get into the game. So is it true, or is it a con? Can stem cells from plants benefit your skin, and if so how? Is stem cell just a buzz word that unscrupulous marketers use to dupe you into thinking they are scientifically on the leading edge?

Plant Stem Cell Basics

A fertilized ovum (egg) is the ultimate stem cell. Every animal and plant that reproduces sexually begins as a fertilized ovum, with half of its genetic material contributed by the male parent and half from the female parent. In the case of flowering plants, structures within the flower play both roles. Pollen from the stamen is the equivalent of animal sperm and the pistol is the female receptive organ. A stem cell with the ability to repeatedly sub-divide and eventually differentiate into all types of cells found within an individual animal or plant is termed totipotential.

In the animal kingdom, a fertilized ovum divides, creating daughter totipotential stem cells, for only about four days. Daughter cells subsequently differentiate into pluripotential stem cells, which can differentiate into different various types of cells, but not all types. Plants, on the other hand, have totipotential stem cells throughout their life. These cells can develop into a complete adult plant.

Totipotential plant stem cells exist in very small numbers and are found in highly specialized tissues, structures called meristems. Meristems exist in root and shoot sprouts and are the cells from which all other plant cells and structures originate. Every root and stem shoot tip contains a very small number of these extraordinarily important cells. Meristems in shoot sprouts are called apical meristems, and those on the tips of roots are called root meristems. Remove the meristem and all growth in that part of the plant ceases.

Meristem stem cells are under external control and respond to local humoral factors from adjacent cells (quiescent cells) as well as more systemic plant hormones called cytokinin and auxin. Apical and root meristems have different specific, but complementary, controlling mechanisms. Generally speaking, hormonal influences that make an apical meristem grow may be inhibitory to root meristems, and vice versa. It is an intricately coordinated process in which stem cell activity is very tightly controlled and the number of totipotential stem cells is maintained at a very sparse population in comparison to the total plant cellular number.

Of paramount interest for this discussion is the fact that both apical and root meristems have control systems that act upon them, which are controlled by the needs of the entire plant. Without these outside influences, the cells in the meristem do not divide to produce daughter cells. While indispensable for plant growth, meristem stem cells are incapable of function without external influences dictating their response. These cells are followers, not leaders.

The photos show the relative size of structures within the meristem regions of a growing plant.

In the first photo (at right), the stem cells within the root meristem and adjacent quiescent cells are colored blue. The root meristem is also extremely tiny, consisting of only a few, albeit very important cells.

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Botanical Stem Cells in Skin Care | BareFacedTruth.com