StemCell Therapy

Boston, MA (PRWEB) December 23, 2014

Earlier this year in a June 24 international conference presentation, Dr. James L. Sherley, director of the Adult Stem Cell Technology Center, LLC (ASCTC) focused attention on an often overlooked and under appreciated unique property of adult tissue stem cells. His title Asymmetric Self-Renewal by Distributed Stem Cells: Misunderstood in the Past, Important for the Future, embodied the essence of his message to congress participants. He gave the address at the 4th World Congress on Cell Science and Stem Cell Research in Valencia, Spain.

The international congress was organized by the Omics Group as a part of its mission to foster the dissemination of leading discoveries and advances in life sciences research. Their posting this month of the slides from Dr. Sherley's June 24 keynote address now provides worldwide open access to life sciences investigators - stem cell biologists in particular - of the concepts that he emphasized.

In a 2008 publication [Breast Disease 29, 37-46, 2008], Sherley coined the new term distributed stem cells (DSCs) as a biology-based name for all natural tissue stem cells that are not embryonic in origin. Adult stem cells are included under the DSC heading. DSCs do not make every cell in the body. Their nature is to produce only a limited tissue-specific or organ-specific distribution of the total possible mature cell types. So, for example, liver DSCs make mature liver cells, but not mature cells found in other organs like the lungs.

Since 2001 and the start of "the stem cell debate," Sherley has insisted that only DSCs can be effective for developing new cellular therapies. In his keynote address, he explained to attendees why the counterparts of DSCs human embryonic stem cells (hESCs) and more recently developed induced pluripotent stem cells (iPSCs) could not.

Though many stem cell scientists recognize and acknowledge the genetic defects, incomplete differentiation, and tumor formation problems of hESCs and iPSCs - which their proponents suggest can be solved - few appreciate their greater problem, which cannot be solved. Unlike DSCs, hESCs and iPSCs lack the property of asymmetric self-renewal.

Sherleys main message is that asymmetric self-renewal, which is the gnomonic for DSCs the very property that defines DSCs is essential for effective cellular therapies. Asymmetric self-renewal means that DSCs can actively multiply with simultaneous reproduction of themselves and production of mature cells. This ability allows DSCs to replenish mature cells, which are continuously lost from tissues and organs, but not lose their genetic blueprint required for tissue and organ renewal and repair.

The asymmetric self-renewal of DSCs is a crucial consideration for all aspects of their study and use. Sherley argues that overlooking it is holding back progress in regenerative medicine. Asymmetric self-renewal is the factor that limits the production of DSCs; but it is so unique to them that it can also be used to identify DSCs, which are notorious for being elusive. The ASCTCs patented technologies for producing and counting DSCs for research and clinical development are grounded in the companys special research and bioengineering expertise for DSC asymmetric self-renewal.

Asymmetric self-renewal may even play a role in the efficient production of iPSCs. At the end of his address, Sherley announced the approval of a new ASCTC patent. The patent covers the invention of a method to make iPSCs from DSCs that were produced by regulating their asymmetric self-renewal (U.S. Patent and Trademark Office No. 8,759,098).

The ASCTC anticipates that despite the new technologys origin in DSC research, it will advance human disease research based on iPSCs. Although iPSCs are not suitable for cell therapy applications, they are uniquely able to provide disease research models for hard to obtain cell types found in patients (e.g., brain cells from autism patients, cardiac cells from heart disease patients).

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Adult Stem Cell Technology Center, LLCs Director Sherley's Address on Whats Holding Back Regenerative Medicine ...

(New York City) A new test may reveal which patients will respond to treatment for graft versus host disease (GVHD), an often life-threatening complication of stem cell transplants (SCT) used to treat leukemia and other blood disorders, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published online today in the journal Lancet Haematology and in print in the January issue.

Patients with fatal blood cancers like leukemia often require allogenic stem cell SCT to survive. Donor stem cells are transplanted to a recipient, but not without the risk of developing GVHD, a life-threatening complication and major cause of death after SCT. The disease, which can be mild to severe, occurs when the transplanted donor cells (known as the graft) attack the patient (referred to as the host). Symptom severity, however, does not accurately define how patients will respond to treatment and patients are often treated alike with high-dose steroids. Although SCT cures cancer in 50 percent of the patients, 25 percent die from relapsed cancer and there remaining go into remission but later succumb to effects of GVHD.

"High dose steroids is the only proven treatment for GVHD," said James L. M. Ferrara, MD, DSc, Ward-Coleman Chair in Cancer Medicine Professor at the Icahn School of Medicine at Mount Sinai, Director of Hematologic Malignancies Translational Research Center at Tisch Cancer Institute at Mount Sinai. "Those with low-risk GVHD are often over-treated and face significant side-effects from treatment. Patients with high risk GVHD are undertreated and the GVHD progresses, often with fatal consequences. Our goal is to provide the right treatment for each patient. We hope to identify those patients at higher risk and design an aggressive intervention while tailoring a less-aggressive approach for those with low-risk."

Dr. Ferrara, along with a multi-center team of researchers, developed and tested this new scoring system using almost 500 patient blood samples with newly diagnosed GVHD in varying grades from two different centers. They used three validated biomarkers TNFR1, ST2 and Reg3 to create an algorithm that calculated the probability of non-relapse mortality (usually caused by GVHD) that provided three distinct risk scores to predict the patient's response to GVHD treatment.

The acid test was to evaluate the algorithm in a validation set of 300 additional patients from twenty different SCT centers throughout the US. The algorithm worked perfectly, and the cumulative incidence of non-relapse mortality significantly increased as the GVHD score increased, and so the response rate to primary GVHD treatment decreased.

"This new scoring system will help identify patient who may not respond to standard treatments, and may require an experimental and more aggressive approach," said Dr. Ferrara. "And it will also help guide treatment for patients with lower-risk GVHD who may be over-treated. This will allow us to personalize treatment at the onset of the disease. Future algorithms will prove increasingly useful to develop precision medicine for all SCT patients."

In order to capitalize on this discovery, Dr. Ferrara has created the Mount Sinai Acute GVHD International Consortium (MAGIC) which consists of a group of ten SCT centers in the US and Europe who will collaborate to use this new scoring system to test new treatments for acute GVHD. Dr. Ferrara and colleagues have also written a protocol to treat high-risk GVHD that has been approved by the FDA.

###

Co-collaborators included University of Michigan, University of Regensburg, and the Blood and Marrow Clinical Trials Network.

The study was supported by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Doris Duke Charitable Fund, the American Cancer Society, and the Judith Devries Fund.

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The potential of SCs to replace dead or damaged cells in any tissue of the body heralds the advent of a new field of medicine that is delivering cures for diseases now thought to be untreatable

Stem cell therapy represents a promising avenue for the treatment of disorders like

Q1: What are stem cells? Answer: Stem cells are class of undifferentiated cells that are able to differentiate into specialized cell types .They have the unique properties of self renewal and differentiation. Differentiation property of stem cells help them to form another type of cell with more specialized function such as brain cell, red blood cell or muscle cell and also the entire organ. During the foetal development, cells divide, migrate, specialize and form the organ. After birth, stem cells are also present in bone marrow which can be used to treat various diseases.

Q2: Which disorders can be treated using Stem Cells? Answer: Currently stem cells are being used successfully to treat various (disorders) diseases like Cerebral palsy, Spinal Cord Injury, Traumatic brain injury, Paralysis, Brain Stroke Osteoarthritis, Autism etc. Apart from this, stem cells can be used to treat liver disorders and Diabetes.

Q3: How is Stem Cell Therapy carried out? Answer: Stem Cell therapy is a very simple and painless process.Mesenchymal stem cells are injected directly into the synivial fluid in the knee. The whole process is carried out very carefully under sterile conditions.

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This treatment will only be allowed under carefully defined conditions, however, so that the outcomes can be carefully monitored to see if the treatment works and doesnt have any unexpected side-effects.

Stem cells can act as a repair system for the body.

Limbal stem cells are located in the eye at the border between the cornea the clear front part of the eye - and the sclera the white of the eye.

Physical or chemical burns can cause loss of these stem cells, resulting in limbal stem cell deficiency, LSCD, a condition that is estimated to affect about 3.3 out of 100,000 people in the European Union and around 650 people in Britain.

Symptoms include pain, sensitivity to light, inflammation, excessive blood vessel growth, clouding of the cornea, and eventually blindness.

In LSCD the limbal stem cells become so diminished that they eyes can no longer make new cells to repair damage.

The new treatment takes a small sample of the patients healthy cornea, removes the stem cells and grows them until there are sufficient numbers to put back into the eye. The cells themselves then repair the damage.

Moorfields Eye Hospital in London has successfully treated around 20 people with Holocar so far in trials.

Prof Chris Mason, from University College London, told the BBC: "This move would enable far more people to access it, you could now prescribe this."

The EMA decision to approve Holoclar will now be sent to the European Commission for market authorization. It will then be up to Nice to decide whether to approve the therapy for use on the NHS.

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Freeport, Grand Bahama (PRWEB) December 18, 2014

Okyanos, the leader in cell therapy, announced the expansion of its medical team to accommodate the growing demand for cell therapy to treat patients with chronic unmet needs for which adult stem cell therapy using cells from a persons own fat (adipose) tissue has been found to be safe and efficacious. Led by a prestigious team of U.S.-licensed physicians and nursing staff, the team includes Dr. Todd Malan, Chief Cell Therapy Officer and pioneer of adipose-derived stem cell therapy, and is joined by Dr. Matthew Mick, Cardiologist, FACC, Fellowship at Cleveland Clinic.

We are very pleased to have such a competent and highly regarded aggregate of expertise, said Okyanos CEO Matt Feshbach. Our team is comprised of leaders in their respective fields, each of whom is committed to bringing about a new standard of care and better quality of life to our patients.

Todd Malan, MD, serves as the Chief Cell Therapy Officer and General Surgeon at Okyanos, overseeing the fat-harvesting and stem cell isolation step of the Okyanos cell therapy process. A pioneer of fat-derived stem cell therapies, he became the first physician in the U.S. to utilize stem cells from fat for soft tissue reconstruction in October 2009, combining water-assisted fat-harvesting, fat transfer and adult stem cell technologies.

Matthew J. Mick, MD, is a triple board-certified interventional cardiologist. After attending the Indiana University School of Medicine, Dr. Mick completed his Cardiovascular Disease and Interventional Fellowships at the Cleveland Clinic Foundation. Dr. Mick participated as Principal Investigator and Co-Investigator in more than 20 cardiac clinical trials. He was a leader in developing trans-radial cardiac catheterization and holds several patents for cardiac catheters. Dr. Mick has performed over 15,000 diagnostic procedures in his 22 years of practice.

As the Director of Nursing managing a medical team which now numbers 10, Gretchen Dezelick oversees all of the clinical operations and maintains the superior cleanliness and safety standards that help make Okyanos a center of excellence. With more than 25 years of nursing experience progressing from bedside nursing to administrative and management positions in a variety of healthcare settings, Gretchen was a Certified Critical Care Nurse (CCRN) for more than 20 years and has been a Certified Peri-Operative Nurse (CNOR) for more than three years as well as being a Licensed Health Care Risk Manager (LHCRM).

Okyanos is also very proud to include several Bahamian medical staff such as Anesthesiologist Dr. Vincent Burton, Fellow of the Royal College of Anaesthetists, UK (FRCA), a Certified Critical Care Nurse, cardiology tech, sonographer, surgical scrub tech and a facilities tech, to deliver well-rounded expert patient care. The team also includes a Certified Cardiovascular Nurse, a BSN RN and a cardiovascular tech, providing more than 88 years of combined experience.

Okyanos follows the treatment guidelines laid out in clinical trials such as PRECISE and others which have demonstrated positive results from adult stem cell therapy. Okyanos cell therapy is performed in their newly constructed surgery center built to U.S. surgical standards and which also includes a state-of-the-art Phillips cath lab.

Adult stem cell therapy has emerged as a new treatment alternative for those who are restricted in activities they can no longer do but are determined to live a more normal life. Okyanos cell therapy uses a unique blend of adult stem cells derived from a patients own fat tissue, thereby helping the bodys own natural biology to heal itself.

Just 50 miles from 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 autoimmune diseases, tissue ischemia, neurological and orthopedic conditions.

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PHILADELPHIA As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

The research was supported by the National Institutes of Health (R01-AR054593, P30-AR057217)

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Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Newswise PHILADELPHIA - As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

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