Stem Cell Clinic

Stem cell transplantation for severe sclerosis associated with improved long-term survival

By Stem Cell Treatment

PUBLIC RELEASE DATE:

24-Jun-2014

Contact: Jacob M. van Laar j.m.vanlaar@umcutrecht.nl The JAMA Network Journals

Among patients with a severe, life-threatening type of sclerosis, treatment with hematopoietic stem cell transplantation (HSCT), compared to intravenous infusion of the chemotherapeutic drug cyclophosphamide, was associated with an increased treatment-related risk of death in the first year, but better long-term survival, according to a study in the June 25 issue of JAMA.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy (a disorder of the blood vessels), low-grade inflammation, and fibrosis (development of excess fibrous connective tissue) in skin and internal organs. Previously, small studies have shown that systemic sclerosis is responsive to treatment with autologous HSCT, although it has been unclear whether HSCT improves survival, according to background information in the article. For this study, autologous HSCT involved a multistep process beginning with infusion of high doses of cyclophosphamide and an antibody against immune cells, followed by reinfusion of the patient's own stem cells that had been previously collected from blood and purified.

Jacob M. van Laar, M.D., Ph.D., of the University Medical Center Utrecht, Utrecht, the Netherlands and Dominique Farge M.D., Ph.D, of the Assistance Publique - Hopitaux de Paris, Paris 7 Diderot University, France, and colleagues randomly assigned 156 patients with early diffuse cutaneous (widespread skin involvement) systemic sclerosis to receive HSCT (n = 79) or cyclophosphamide (n = 77; 12 monthly infusions). The phase 3 clinical trial was conducted in 10 countries at 29 centers; patients were recruited from March 2001 to October 2009 and followed up until October 2013.

During a median follow-up of 5.8 years, 53 adverse events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). Patients treated with HSCT experienced more adverse events (including death) in the first year but had better long-term event-free survival than those treated with cyclophosphamide.

Patients in the HCST group experienced higher mortality in the first year but had better long-term overall survival than those treated with cyclophosphamide. During year 1 there were 11 deaths (13.9 percent, including 8 treatment-related deaths) in the HSCT group vs 7 (9.1 percent, no treatment-related deaths) in the control group. After year 2 of follow-up, there were 12 deaths (15.2 percent) in the HSCT group vs 13 (16.9 percent) in the control group. After 4 years of follow-up, there were 13 deaths (16.5 percent) in the HSCT group vs 20 (26.0 percent) in the control group.

The authors add that HSCT was also more effective than intravenous cyclophosphamide on measures evaluating skin, functional ability, quality of life, and lung function, consistent with previous studies.

"Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit," the authors conclude.

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Stem cell transplantation for severe sclerosis associated with improved long-term survival

Stem Cell Transplantation For Severe Sclerosis Linked With Improved Long-term Survival

By Stem Cell Treatment

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Newswise Among patients with a severe, life-threatening type of sclerosis, treatment with hematopoietic stem cell transplantation (HSCT), compared to intravenous infusion of the chemotherapeutic drug cyclophosphamide, was associated with an increased treatment-related risk of death in the first year, but better long-term survival, according to a study in the June 25 issue of JAMA.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy (a disorder of the blood vessels), low-grade inflammation, and fibrosis (development of excess fibrous connective tissue) in skin and internal organs. Previously, small studies have shown that systemic sclerosis is responsive to treatment with autologous HSCT, although it has been unclear whether HSCT improves survival, according to background information in the article. For this study, autologous HSCT involved a multistep process beginning with infusion of high doses of cyclophosphamide and an antibody against immune cells, followed by reinfusion of the patient's own stem cells that had been previously collected from blood and purified.

Jacob M. van Laar, M.D., Ph.D., of the University Medical Center Utrecht, Utrecht, the Netherlands and Dominique Farge M.D., Ph.D, of the Assistance Publique - Hopitaux de Paris, Paris 7 Diderot University, France, and colleagues randomly assigned 156 patients with early diffuse cutaneous (widespread skin involvement) systemic sclerosis to receive HSCT (n = 79) or cyclophosphamide (n = 77; 12 monthly infusions). The phase 3 clinical trial was conducted in 10 countries at 29 centers; patients were recruited from March 2001 to October 2009 and followed up until October 2013.

During a median follow-up of 5.8 years, 53 adverse events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). Patients treated with HSCT experienced more adverse events (including death) in the first year but had better long-term event-free survival than those treated with cyclophosphamide.

Patients in the HCST group experienced higher mortality in the first year but had better long-term overall survival than those treated with cyclophosphamide. During year 1 there were 11 deaths (13.9 percent, including 8 treatment-related deaths) in the HSCT group vs 7 (9.1 percent, no treatment-related deaths) in the control group. After year 2 of follow-up, there were 12 deaths (15.2 percent) in the HSCT group vs 13 (16.9 percent) in the control group. After 4 years of follow-up, there were 13 deaths (16.5 percent) in the HSCT group vs 20 (26.0 percent) in the control group.

The authors add that HSCT was also more effective than intravenous cyclophosphamide on measures evaluating skin, functional ability, quality of life, and lung function, consistent with previous studies.

Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit, the authors conclude. (doi:10.1001/jama.2014.6368; Available pre-embargo to the media at http://media.jamanetwork.com)

Editors Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Stem Cell Transplantation For Severe Sclerosis Linked With Improved Long-term Survival

Immediate closure of Arroyo stem cell doctor's clinic ordered

By Stem Cell Treatment

CLOSURE. The Tagaytay City Office of the Mayor orders the immediate closure of the Green & Young Health & Wellness Center. Photo by Jee Geronimo/Rappler

MANILA, Philippines The clinic in Tagaytay City where former President Gloria Macapagal-Arroyo sought alternative treatment in 2012 but whose doctor was recently exposed to be unlicensed has been ordered to close down.

In a resolution dated May 29, the office of Mayor Agnes Tolentino directed Antonia Park to immediately stop the operation of her clinic which was listed as a massage clinic/sauna/turkish/swedish bath.

The resolution listed down adequate, relevant evidence that Park unlawfully used and practiced medicine in her clinic. It cited the following in revoking Green & Young Health & Wellness Center's business permit:

The above evidence were based on several affidavits, a Professional Regulatory Commission document which showed Park is not authorized to practice medicine in the country, and a 2012 statement from Park regarding the condition of and alternative treatment for Arroyo.

In July 2012, Park took in Arroyo for possible stem cell therapy. Park used the title MD in her statement released to the press. (READ: Fourth stem cell treatment for Arroyo)

Republic Act 2382 or The Medical Act of 1959 considers a person as engaged in the practice of medicine when he/she uses MD after his/her name.

ILLEGAL PRACTICE. Dr Antonia Park in this Nov 17, 2012 photo taken by Kate Tan. Photo from Bernard Tan.

Since Park herself admitted she is not a registered physician in the Philippines, any act constituting practice of medicine will be considered as violative of the law.

The Office of the Mayor said in the resolution it found sufficient ground for the revocation of the business permit and the closure of the establishment.

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Immediate closure of Arroyo stem cell doctor's clinic ordered

Scientists identify link between stem cell regulation and the development of lung cancer

By Stem Cell Medicine

PUBLIC RELEASE DATE:

19-Jun-2014

Contact: Shaun Mason smason@mednet.ucla.edu 310-206-2805 University of California - Los Angeles

UCLA researchers led by Dr. Brigitte Gomperts have discovered the inner workings of the process thought to be the first stage in the development of lung cancer. Their study explains how factors that regulate the growth of adult stem cells that repair tissue in the lungs can lead to the formation of precancerous lesions.

Findings from the three-year study could eventually lead to new personalized treatments for lung cancer, which is responsible for an estimated 29 percent of U.S. cancer deaths, making it the deadliest form of the disease.

The study was published online on June 19 in the journal Stem Cell. Gomperts, a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the UCLA Jonsson Comprehensive Cancer Center, collaborated with Manash Paul and Bharti Bisht, postdoctoral scholars and co-lead authors of the study.

Adult stem cells in lung airways are present specifically to repair the airways after injury or disease caused by smoking, pollution, viruses or other factors. Gomperts and her team found that this reparative process is tightly regulated by molecules called reactive oxygen species, or ROS.

Recent research has shown that low levels of ROS are important for signaling the stem cells to perform important functions such as repairing tissue damage while high levels of ROS can cause stem cells to die. But the level of ROS needed for repair to be initiated has remained a subject of debate among researchers.

The UCLA study found that the dynamic flux of ROS from low to moderate levels in the airway stem cells is what drives the repair process, and that the increase in ROS levels in the repairing cell is quickly reduced to low levels to prevent excessive cell proliferation.

Gomperts' lab found that disrupting this normal regulation of ROS back to low levels is equivalent to pulling the brakes off of the stem cells: They will continue to make too many of themselves, which causes the cells not to mature and instead become precancerous lesions. Subsequent progressive genetic changes to the cells in these lesions over time can eventually allow cancerous tumors to form.

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Scientists identify link between stem cell regulation and the development of lung cancer

The Adult Stem Cell Technology Center, LLC Announces Patent for Induced Pluripotent Stem Cells Produced with a Single …

By Stem Cell Medical Center

Valencia, Spain (PRWEB) June 24, 2014

Today at Cell Science-2014 in Valencia, Spain, Dr. James L. Sherley, Director of Bostons Adult Stem Cell Technology Center, LLC, announced the issue of another significant patent to the companys growing portfolio of adult tissue stem cell intellectual property. The new patent issued today (U.S. Patent and Trademark Office No. 8,759,098) protects a method for producing induced pluripotent stem cells (iPSCs) with a single non-genetic agent.

Director Sherley made the announcement at the conclusion of his keynote address at the 4th Annual World Congress on Cell Science and Stem Cell Research. After discussing unique aspects of adult stem cells that are often overlooked, he highlighted a proposed connection between adult stem cells and iPSCs that was the basis for the newly patented biotechnology.

iPSCs are currently the subject of intense biological and biomedical research. These artificially produced stem cells provide the research capabilities of human embryonic stem cells (hESCs). But since their production does not involve human embryos, iPSCs do not pose ethical concerns. However, because of their genetic defects and propensity for forming tumors, also like hESCs, it is unlikely that iPSCs will ever be of sufficient quality and safety for use in regenerative medicine therapies.

Despite the problems preventing direct application of iPSCs for medical therapies, their use to develop biological surrogate cells for difficult-to-obtain cells for diseased human tissues for research is unparalleled (e.g., living brain cells from children with autism). For this reason, new technologies, like those represented by the ASCTCs new patent, are important for leading the way to more efficient production of higher quality iPSCs.

Unlike the recently discredited reports of acidic conditions as a single non-genetic agent for producing iPSCs, the ASCTCs technology has a well-established historical record and biological rationale. The method was originally proposed in the National Institutes of Health (NIH) Directors Pioneer Award research of ASCTC Director Sherley, when he was a research professor at the Massachusetts Institute of Technology.

The active agent, xanthine, is a naturally occurring normal compound found in the bodys blood and tissues. In earlier ASCTC studies, xanthine was shown active for expanding adult tissue stem cells. Xanthine is a member of a class of compounds called purines that regulate the action of a well-known cancer-protective gene called p53. The p53 gene has also been shown by several laboratories to be an important factor in the efficiency of iPSC cell production.

For the ASCTC technology, xanthine-expanded adult tissue stem cells are placed in commonly used iPSC culture medium supplemented with xanthine as the only additive. The usual introduction of specific genes or their experimental manipulation is not required. The new single-agent technology yields iPSCs at efficiencies similar to methods that require direct genetic manipulation.

The ASCTCs iPSC production technology was described in an earlier issue of the Journal of Biomedicine and Biotechnology (Par, J.-F., and Sherley, J. L. 2011. Culture Environment-Induced Pluripotency of SACK-Expanded Tissue Stem Cells, J. Biomed. Biotechnol. vol. 2011, Article ID 312457, 12 pp., 2011. doi:10.1155/2011/312457). Thus far, the method has only been applied to purine-expanded mouse pancreatic tissue stem cells. It also has not been evaluated for combined effects with other iPSC production methods. Director Sherley notes that, wider evaluation of the new technology will help to establish its range as an advantageous new reagent for producing higher quality iPSCs more efficiently.

************************************************************************************************************* The Adult Stem Cell Technology Center, LLC (ASCTC) is a Massachusetts life sciences company established in September 2013. ASCTC director and founder, James L. Sherley, M.D., Ph.D. is the foremost authority on the unique properties of adult stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for cell medicine and drug development. Currently, ASCTC is employing its technological advantage to pursue commercialization of mass-produced therapeutic human liver cells and facile assays for screening-out drug candidates that are toxic to adult tissue stem cells.

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The Adult Stem Cell Technology Center, LLC Announces Patent for Induced Pluripotent Stem Cells Produced with a Single ...

Time-lapse study reveals bottlenecks in stem cell expansion

By Uncategorized

PUBLIC RELEASE DATE:

12-Jun-2014

Contact: Hannah Postles h.postles@sheffield.ac.uk 01-142-221-046 University of Sheffield

A time-lapse study of human embryonic stems cells has identified bottlenecks restricting the formation of colonies, a discovery that could lead to improvement in their use in regenerative medicine.

Biologists at the University of Sheffield's Centre for Stem Cell Biology led by Professor Peter Andrews and engineers in the Complex Systems and Signal Processing Group led by Professor Daniel Coca studied human pluripotent stem cells, which are a potential source of cells for regenerative medicine because they have the ability to produce any cell type in the body.

However, using these stem cells in therapies is currently hampered by the fact they can acquire genetic changes during prolonged culture which are non-random and resemble mutations in cancer cells.

Researchers used time-lapse imaging of single human embryonic stem cells to identify aspects of their behaviour that restrict growth and would be targets for mutations that allow cells to grow more efficiently.

Dr Ivana Barbaric, from the University of Sheffield's Department of Biomedical Science, said: "We study pluripotent stem cells, which have huge potential for use in regenerative medicine due to their ability to become any cell in the human body. A pre-requisite for this is maintaining large numbers of undifferentiated cells in culture. However, there are several obstacles such as cells tend to die extensively during culturing and they can mutate spontaneously. Some of these genetic mutations are known to provide stem cells with superior growth, allowing them to overtake the culture a phenomenon termed culture adaptation, which mimics the behaviour of cancer cells.

"In order for pluripotent stem cells to be used safely in regenerative medicine we need to understand how suboptimal culture conditions, for example culturing cells at low split ratios, affect the cells and can lead to culture adaptation."

The team's research combined the use of time-lapse microscopy, single-cell tracking and mathematical modelling to characterise bottlenecks affecting the survival of normal human embryonic stem cells and compared them with adapted cells.

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Time-lapse study reveals bottlenecks in stem cell expansion

Promising T cell therapy

By Uncategorized

PUBLIC RELEASE DATE:

17-Jun-2014

Contact: Vera Siegler vera.siegler@tum.de 49-892-892-2731 Technische Universitaet Muenchen

This news release is available in German.

The cells of the human immune system are created from special stem cells in the bone marrow. In diseases affecting the bone marrow, such as leukemia, the degenerate cells must be destroyed using radiation or chemotherapy. Subsequently, the hematopoietic system has to be replaced with stem cells from the blood of a healthy donor. Because of the resulting temporary weakening of the immune system, patients are more exposed to viruses that would normally be warded off.

The cytomegalovirus (CMV), which can cause serious damage to lungs or liver in persons with a weakened defense, poses a major clinical problem. In healthy human beings, a CMV infection will usually not produce any symptoms, since the virus is kept at bay by specific immune cells. In their work, the scientists were able to demonstrate that the transfer of just a few specific immune cells is sufficient to protect the recipient with the weakened immune system against infections. To do this, they used T cells that can recognize and kill specific pathogens.

Tested in an animal model

Dr. Christian Stemberger, first author of the study, and his colleagues, first isolated T cells from the blood of healthy donor mice. These immune cells were directed against molecular elements of a bacterial species which normally causes severe infections in animals. The T cells were then transferred to recipient mice that, due to a genetic modification, could no longer produce immune cells of their own similarly to patients suffering from leukemia.

Following the T cell transfer, the researchers infected the treated recipient mice with the bacteria. The results showed that the animals now have effective immune protection against the pathogens, preventing them from becoming ill. "The most astonishing result was that the offspring cells of just one transferred donor cell were enough to completely protect the animals," Christian Stemberger explains.

Successfully used in patients

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Promising T cell therapy

Stem cell mobilization therapy may effectively treat osteoarthritis

By Stem Cell Treatment

PUBLIC RELEASE DATE:

19-Jun-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (June 19, 2014) Researchers in Taiwan have found that peripheral blood stem cells "mobilized" by a special preparation of granulocyte colony-stimulating factor (G-CSF) prior to their injection into rats modeling osteoarthritis (OA), stimulated the bone marrow to produce stem cells, leading to the inhibition of OA progression. The finding, they said, may lead to a more effective therapy for OA, a common joint disease that affects 10 percent of Americans over the age of 60.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1109Deng.

"Currently, OA treatment involves the use of anti-inflammatory drugs, analgesics, lubricating supplements, or surgery," said study lead author Dr. Shih-Chieh Hung of the Department of Medical Research and Education at the Taipei Veterans general Hospital in Taiwan. "Recently, hematopoietic (blood) stem cells derived from bone marrow have emerged as a potential treatment for OA. We hypothesized that G-CSF-mobilized peripheral blood stem cells (gm-PBSCs) contain a population of primitive stem cells that have the capacity for mobility once released from stem cell niches."

While the beneficial effects of G-CSF-mobilized peripheral blood stem cells have been documented when used for treating the negative effects of chemotherapy and radiation, as well as peripheral arterial diseases, this is the first study to investigate the use of gm-PBSCs to treat skeletal diseases, such as OA.

"We demonstrated that PBSCs, mobilized by G-CSF and infused for five days in rats modelling OA, provided a number of beneficial results, including increasing cluster of differentiation 34 positive (CD34+) cell percentages up to 55 fold," reported the authors. "Further, we demonstrated that the progression of OA was inhibited by the gm-PBSCs."

The researchers noted that the use of G-CSF administration in humans to treat other diseases and conditions has been found to be "safe and effective," despite known side effects such as bone pain, headache, fatigue, and nausea which, they added, are generally "transient, self-limiting and without long-term consequences."

"Although potential long-term adverse effects, such as malignancy after G-CSF administration have been reported, the frequency is low and the relationship between major adverse effects and G-CSF administration is not clear," said Dr. Hung.

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Stem cell mobilization therapy may effectively treat osteoarthritis

Stem cell-based transplantation approach improves recovery from stroke

By Stem Cell Treatment

PUBLIC RELEASE DATE:

19-Jun-2014

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

Stroke is a leading cause of death and disability in developed countries, and there is an urgent need for more clinically effective treatments. A study published by Cell Press June 19th in Stem Cell Reports reveals that simultaneous transplantation of neural and vascular progenitor cells can reduce stroke-related brain damage and improve behavioral recovery in rodents. The stem cell-based approach could represent a promising strategy for the treatment of stroke in humans.

"Our findings suggest that early cotransplantation treatment can not only replace lost cells, but also prevent further deterioration of the injured brain following ischemic stroke," says senior study author Wei-Qiang Gao of Shanghai Jiaotong University. "With the development of human embryonic and induced pluripotent stem cell technology, we are optimistic about the potential translation of our research into clinical use."

The most common kind of stroke, known as ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain. Although a medicine called tissue plasminogen activator can break up blood clots in the brain, it must be given soon after the start of symptoms to work, and there are no other clinically effective treatments currently available for this condition. Stem cell transplantation represents a promising therapeutic strategy, but transplantation of either neural progenitor cells or vascular cells has shown restricted therapeutic effectiveness.

In the new study, Gao teamed up with colleagues at Shanghai Jiao Tong University, including Jia Li, Yaohui Tang, and Guo-Yuan Yang, to test whether cotransplantation of both neural and vascular precursor cells would lead to better outcomes. They induced ischemic stroke in rats and then simultaneously injected neural and vascular progenitor cells from mice into the stroke-damaged rat brains 24 hours later. The transplanted precursor cells turned into all major types of vascular and brain cells, including mature, functional neurons. The resulting vascular cells developed into microvessels, while the grafted neural cells produced molecules known to stimulate the growth of both neurons and vessels.

"This is the first study to use embryonic stem cell-derived vascular progenitor cells together with neural progenitor cells to treat ischemic stroke," Gao says. "These two types of progenitors generate nearly all types of brain cells, including endothelial cells, pericytes/smooth muscle cells, neurons, and astrocytes, resulting in better restoration of neurovascular units and better replacement of the lost cells in the stroke model. A previously reported cotransplantation approach published in the journal Stem Cells in 2009 (doi: 10.1002/stem.161) was limited because it did not use vascular precursor cells capable of turning into all major types of vascular cells important for recovery. Our findings here suggest that cotransplantation of the two types of cells that restore the neurovascular unit more effectively is a better approach for the treatment of ischemic stroke."

Two weeks after stroke, rats that had undergone cotransplantation showed less brain damage and improved behavioral performance on motor tasks compared with rats that had been treated with neural progenitor cells alone. "Our findings suggest that cotransplantation of neural and vascular cells is much more effective than transplantation of one cell type alone because these two cell types mutually support each other to promote recovery after stroke," Gao says.

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