Stem Cell Clinic

Stem cells from fatty tissue show potential for bone repair

By Stem Cell Clinic

BRUSSELS - Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialise the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

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Stem cells from fatty tissue show potential for bone repair

Desperate parents make heart-breaking YouTube appeal to find stem cell donor for one-year-old daughter dying from …

By Stem Cell Doctors

Margot Martini's form of leukaemia is so rare, doctors have only seen three similar cases in the last decade

The parents of a one-year-old girl dying from an extremely rare form of leukaemia have made a desperate global appeal to find her a stem cell donor.

Margot Martini was rushed to Great Ormond Street Hospital aged just 14 months last October.

She needed an immediate blood transfusion and spent the next ten days on life support.

Her parents Vicki and Yasser have been told she has a form of leukaemia so rare her consultant has seen only three such cases in the last decade.

They have made a desperate appeal via YouTube in a bid to find a stem cell donor who could save her life.

Yasser told Sky News: "Margot needs to receive a stem cell donation from someone with a similar tissue type as hers. So we are on a worldwide search for a donor - and unfortunately, without much luck to date."

Because Margot's leukaemia is so rare, Margot's parents are organising national "donor drives" where volunteers can register in the hope that someone will be a perfect match.

Anyone who wants to can request a saliva swab kit which can be used at home or register at designated medical centres on three separate "donor days".

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Desperate parents make heart-breaking YouTube appeal to find stem cell donor for one-year-old daughter dying from ...

Stem Cells Could Prove Effective in Treating Brittle Bone Disease

By Stem Cell Medicine

Durham, NC (PRWEB) January 14, 2014

A new study released in STEM CELLS Translational Medicine indicates that stem cells can be effective in treating a debilitating and sometimes lethal genetic disorder called brittle bone disease.

Brittle bone disease, or osteogenesis imperfecta (OI), is characterized by fragile bones causing some patients to suffer hundreds of fractures over the course of a lifetime. In addition, according to the OI Foundation, other symptoms include muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, brittle teeth and short stature. Restrictive pulmonary disease occurs in the more severe cases. Currently there is no cure.

OI can be detected prenatally by ultrasound. In the study reported on in STEM CELLS Translational Medicine, an international team of researchers treated two patients for the disease using mesenchymal stem cells (MSCs) while the infants were still in the womb, followed by stem cell boosts after they were born.

We had previously reported on the prenatal transplantation for the patient with OI type III, which is the most severe form in children who survive the neonatal period, said Cecilia Gtherstrm, Ph.D., of the Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. She and Jerry Chan, M.D., Ph.D., of the Yong Loo Lin School of Medicine and National University of Singapore, and KK Womens and Childrens Hospital, led the study that also included colleagues from the United States, Canada, Taiwan and Australia.

The first eight years after the prenatal transplant, our patient did well and grew at an acceptable rate. However, she then began to experience multiple complications, including fractures, scoliosis and reduction in growth, so the decision was made to give her another MSC infusion. In the two years since, she has not suffered any more fractures and improved her growth.

She was even able to start dance classes, increase her participation in gymnastics at school and play modified indoor hockey, Dr. Gtherstrm added.

The second child, which was experiencing a milder form of OI, received a stem cell transfusion 31 weeks into gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. She followed her normal growth pattern just under the third percentile in height until 13 months of age, when she stopped growing. Six months later, the doctors gave her another infusion of stem cells and she resumed growing at her previous rate.

Our findings suggest that prenatal transplantation of autologous stem cells in OI appears safe and is of likely clinical benefit and that re-transplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive, for which further studies are required, Dr. Chan said.

Although the findings are preliminary, this report is encouraging in suggesting that prenatal transplantation may be a safe and effective treatment for this condition, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Stem Cells Could Prove Effective in Treating Brittle Bone Disease

New breast cancer stem cell findings explain how cancer spreads

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

14-Jan-2014

Contact: Nicole Fawcett nfawcett@umich.edu 734-764-2220 University of Michigan Health System

ANN ARBOR, Mich. Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers. Their finding sheds new light on the process that makes cancer a deadly disease.

"The lethal part of cancer is its metastasis so understanding how metastasis occurs is critical," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the University of Michigan Comprehensive Cancer Center. "We have evidence that cancer stem cells are responsible for metastasis they are the seeds that mediate cancer's spread. Now we've discovered how the stem cells do this."

First, on the outside of the tumor, a type of stem cell exists in a state called the epithelial-mesenchymal transition (EMT) state. These stem cells appear dormant but are very invasive and able to get into the bloodstream, where they travel to distant parts of the body.

Once there, the stem cells transition to a second state that displays the opposite characteristics, called the mesenchymal-epithelial transition state (MET). These cells are capable of growing and making copies of themselves, producing new tumors.

"You need both forms of cancer stem cells to metastasize and grow in distant organs. If the stem cell is locked in one or the other state, it can't form a metastasis," Wicha says.

The findings, which are published in the January issue of Stem Cell Reports, raise a number of questions about how to treat or prevent metastatic breast cancer. Researchers must now understand whether new therapies must attack both forms of the stem cell to be successful. Different pathways regulate each type of stem cell, which suggests that effective therapies must be able to target multiple pathways.

In addition, current tests that look at tumor cells circulating in the blood to help determine whether the cancer is spreading do not appear to capture the EMT stem cells, which are the cancer cells that travel through the blood. U-M researchers are working with colleagues from the U-M College of Engineering to develop new tools to isolate the EMT stem cells from the blood of cancer patients.

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New breast cancer stem cell findings explain how cancer spreads

Panama’s First Umbilical Cord Stem Cell Clinical Trial for Rheumatoid Arthritis Approved by Comité Nacional de …

By Stem Cell Medical Center

Panama City, Panama (PRWEB) January 14, 2014

Translational Biosciences, a subsidiary of Medistem Panama has received the countys first clinical trial approval for the treatment of rheumatoid arthritis with human umbilical cord-derived mesenchymal stem cells (MSC) from the Comit Nacional de Biotica de la Investigacin Institutional Review Board (IRB).

Rheumatoid Arthritis (RA) is an autoimmune disease in which the patients immune system generates cellular and antibody responses to various components of the joint such as type I collagen. As a result of this immune response, not only does joint destruction occur, but also other secondary complications such as pulmonary fibrosis, renal damage, and even heart damage. RA affects approximately 0.5-1% of the population in the United States.

Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve RA symptoms. Because they are immune privileged, the recipients immune system does not reject them. These properties make MSC interesting candidates for the treatment of rheumatoid arthritis and other autoimmune disorders.

Each patient will receive five intravenous injections of umbilical cord stem cells over the course of 5 days. They will be assessed at 3 months and 12 month primarily for safety and secondarily for indications of efficacy.

The stem cell technology being utilized in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panamas 8000 sq. ft. laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.

The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute.

While this is just the first step, it is our hope that Panamas rapid emergence as a leader in applied stem cell research will lead to safe, effective treatments for debilitating diseases such as rheumatoid arthritis and serve to benefit all Panamanians who suffer from it in the not-too-distant future, said Ruben Berocal, M.D., National Secretary of Science, Technology and Innovation (SENACYT). Oversight by the National Committee for Investigational Bioethics ensures patient safety by demanding ethical transparency and compliance with the highest levels of international standards, he added.

For detailed information about this clinical trial visit http://www.clinicaltrials.gov. If you are a rheumatoid arthritis patient who has not responded to disease modifying anti-rheumatic drugs (DMARD) for at least 6 months you may qualify for this trial. Please email trials(at)translationalbiosciences(dot)com for more information about how to apply.

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Panama’s First Umbilical Cord Stem Cell Clinical Trial for Rheumatoid Arthritis Approved by Comité Nacional de ...

New tool assists stem cell therapy

By Uncategorized

Published:Tuesday, January 14, 2014

Updated:Tuesday, January 14, 2014 18:01

A new tool that could help facilitate future stem cell therapy has recently been identified by a UVM professor and his colleagues, according to UVMs College of Medicine.

The development of this tool could potentially help more than 700,000 Americans who suffer a heart attack each year.

Because stem cells have the potential to develop into a variety of cell types in the body, they may offer a renewable source of replacement cells to treat diseases, conditions and disabilities, and even regenerate damaged tissue and organs.

However, the field of regenerative medicine has struggled to successfully graft cells from culture back into injured tissue.

UVM Associate Professor of Medicine Jeffrey Spees, Ph.D., collaborated with the Center for Gene Therapy at Tulane University. His research team recently set out to develop ways to enhance graft success.

Dr. Spees and his team focused on a type of bone marrow-derived progenitor cell or biological cell that forms stromal cells or connective tissue cells.

They found that the medium contained Connective Tissue Growth Factor (CTGF) and the hormone insulin, and together, they have a synergistic effect, Spees said to UVMs College of Medicine.

The group found that the protective ligands resulted in improved graft success, breaking the record for engraftment.

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New tool assists stem cell therapy

The International Society for Stem Cell Research announces its 2014 award recipients

By Stem Cell Treatment

PUBLIC RELEASE DATE:

14-Jan-2014

Contact: Michelle Quivey mquivey@isscr.org 224-592-5012 International Society for Stem Cell Research

CHICAGO The International Society for Stem Cell Research (ISSCR) has announced the following 2014 award recipients, who will be formally recognized at its 12th Annual Meeting in Vancouver, taking place June 18-21, 2014:

The McEwen Award for Innovation, supported by the McEwen Centre for Regenerative Medicine, recognizes original thinking and groundbreaking research pertaining to stem cells or regenerative medicine that opens new avenues of exploration toward the understanding or treatment of human disease or affliction. The winner receives $100,000 USD. Past winners include James Thomson, Rudolf Jaenisch, Kazutoshi Takahashi and Shinya Yamanaka.

Award recipient Surani is a world leader in the field of epigenetics and the development of the mammalian germ line. His work on early mammalian development led to his involvement in the discovery of genomic imprinting and ongoing contributions to understanding the mechanistic basis of imprinting. Most relevant to stem cell biology, is his work on the cellular and molecular specification of the mammalian germ cell lineage, which impacted the field's understanding of how the germ line is established and the molecular mechanisms responsible for reprogramming the epigenome in order to generate the totipotent state.

"The ISSCR is thrilled to announce the McEwen Award for Innovation, our most prestigious award, will be presented to Azim Surani," Janet Rossant, ISSCR president, said. "His pioneering research, which has changed the face of epigenetics and advanced the field of stem cell biology, is a rare and significant contribution from a single individual."

The ISSCR-BD Biosciences Outstanding Young Investigator Award recognizes exceptional achievements by an ISSCR member and investigator in the early part of their independent career in stem cell research. The winner receives a $7,500 USD personal award and an opportunity to present at the ISSCR Annual Meeting. Past winners include Marius Wernig, Cdric Blanpain, Robert Blelloch, Joanna Wysocka and Konrad Hochedlinger.

Award recipient Greco established a noninvasive method to directly visualize skin stem cell division in real time in living animals the first of its kind for imaging any stem cell. By combining this method with laser ablation and transgenic lineage tracing, she captured previously inaccessible key information on stem cell behavior during tissue maintenance and regeneration. She demonstrated that the niche location of stem cells dictates their fates, the niche is required for tissue maintenance, and that a -catenin-mediated extrinsic mechanism regulates stem cell activation.

"The ISSCR is looking forward to presenting our Outstanding Young Investigator Award to Valentina Greco," Rossant said. "Her enthusiastic nomination by over a dozen leaders in the field of stem cell research demonstrates the significance of her early-career contributions to stem cell biology and regenerative medicine."

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The International Society for Stem Cell Research announces its 2014 award recipients

T-cell research sheds light on why HIV can persist despite treatment

By Stem Cell Treatment

Jan. 14, 2014 Ryan Zurakowski, assistant professor of electrical and computer engineering at the University of Delaware, is co-author of a paper appearing in Nature Medicine on Jan. 12 highlighting the role of T-cells in HIV.

The paper, titled "HIV-1 Persistence in CD4+ T-Cells with Stem Cell-Like Properties," provides evidence that a particular T-cell type may help researchers better understand why HIV can persist despite treatment.

Zurakowski's co-authors include Mathias Lichterfeld, the paper's lead author, and researchers from Massachusetts General Hospital (MGH); Ragon Institute of MGH, the Massachusetts Institute of Technology and Harvard University; the First Affiliated Hospital of China Medical University; Brigham and Women's Hospital; and Howard Hughes Medical Institute.

Zurakowski explained that HIV treatments do not kill infected cells. Instead, they stop the infection of new cells, and rely on the virus itself to kill the infected cells. Unfortunately, some cells infected by the virus -- memory T-cells -- are not killed by the virus.

T-cells are a type of lymphocyte, or white blood cell, produced by the thymus gland, that actively participates in the body's immune response. "Memory" T-cells can live for years, or even decades, providing life-long immunity to previously encountered diseases. They can form "quiescent" infections, which last for years, and cause HIV to rebound whenever a patient stops treatment.

During a decade-long study, the researchers discovered that not all memory T-cells are alike. A subgroup of memory T-cells, called "Stem-Cell Memory T-cells" (Tscm), are different, particularly in their ability to produce daughter cells.

The researchers were able to show that the HIV-infected Tscm cells in patients on HIV therapy decayed more slowly than any other type of T-cell. As a result, after 10 years of therapy, the Tscm cells represented 24 percent of the total HIV infected cell population, despite being only 1 percent of the total T-cell population.

This finding is significant, Zurakowski said, because it demonstrates that Tscm cells are the slowest-decaying portion of the HIV reservoir.

"Over time this particular cell type plays an increasingly significant role in sustaining HIV infection in patients that have remained on therapy," he said.

Zurakowski credits the finding to the diligence of Lichterfeld and the researchers at the Ragon Institute in carefully following the same HIV patients for a decade.

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T-cell research sheds light on why HIV can persist despite treatment

Keeping stem cells pluripotent

By Stem Cell Medicine

PUBLIC RELEASE DATE:

13-Jan-2014

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego

While the ability of human embryonic stem cells (hESCs) to become any type of mature cell, from neuron to heart to skin and bone, is indisputably crucial to human development, no less important is the mechanism needed to maintain hESCs in their pluripotent state until such change is required.

In a paper published in this week's Online Early Edition of PNAS, researchers from the University of California, San Diego School of Medicine identify a key gene receptor and signaling pathway essential to doing just that maintaining hESCs in an undifferentiated state.

The finding sheds new light upon the fundamental biology of hESCs with their huge potential as a diverse therapeutic tool but also suggests a new target for attacking cancer stem cells, which likely rely upon the same receptor and pathway to help spur their rampant, unwanted growth.

The research, led by principal investigator Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, focuses upon the role of the highly conserved WNT signaling pathway, a large family of genes long recognized as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7.

"WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state," said Willert. "If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state."

The researchers proved this by using an antibody-like protein that binds to FZD7, hindering its function. "Once FZD7 function is blocked with this FZD7-specific compound, hESCs are no longer able to receive the WNT signal essential to maintaining their undifferentiated state."

FZD7 is a so-called "onco-fetal protein," expressed only during embryonic development and by certain human tumors. Other studies have suggested that FZD7 may be a marker for cancer stem cells and play an important role in promoting tumor growth. If so, said Willert, disrupting FZD7 function in cancer cells is likely to interfere with their development and growth just as it does in hESCs.

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Keeping stem cells pluripotent

Nature Study Discovers Chromosome Therapy to Correct a Severe Chromosome Defect

By Stem Cell Medical Center

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Newswise Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online today in Nature, used stem cells to correct a defective ring chromosome with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome, said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC, San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective counter measures has evaded scientistsuntil now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion and the other two patients had large terminal deletions in one of their chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

It appears that ring chromosomes are lost during rapid and continuous cell divisions during reprogramming, said Yamanaka. The duplication of the normal chromosome then corrects for that lost chromosome.

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Nature Study Discovers Chromosome Therapy to Correct a Severe Chromosome Defect

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