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

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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

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

Stem cell mobilization therapy may effectively treat osteoarthritis

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

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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Stem cell-based transplantation approach improves recovery from stroke

Embryonic stem cells offer new treatment for multiple sclerosis

PUBLIC RELEASE DATE:

16-Jun-2014

Contact: Colin Poitras colin.poitras@uconn.edu 860-486-4656 University of Connecticut

Scientists in the University of Connecticut's Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.

The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models and offered better treatment results than stem cells derived from human adult bone marrow.

The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.

"The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside," says Professor Marc Lalande, director of the UConn's Stem Cell Institute.

The research was supported by a $1.13 million group grant from the state of Connecticut's Stem Cell Research Program that was awarded to ImStem and Professor Pachter's lab.

"Connecticut's investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research," says Gov. Dannel P. Malloy. "This new study moves us one step closer to a stem cell-based clinical product that could improve people's lives."

The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.

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Embryonic stem cells offer new treatment for multiple sclerosis

Microenvironment of hematopoietic stem cells can be a target for myeloproliferative disorders

The discovery of a new therapeutic target for certain kinds of myeloproliferative disease is, without doubt, good news. This is precisely the discovery made by the Stem Cell Physiopathology group at the CNIC (the Spanish National Cardiovascular Research Center), led by Dr. Simn Mndez-Ferrer. The team has shown that the microenvironment that controls hematopoietic stem cells can be targeted for the treatment of a set of disorders called myeloproliferative neoplasias, the most prominent of which are chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myelogenous leukemia (CML).

The findings, published today in Nature, demonstrate that these myeloproliferative neoplasias only appear after damage to the microenvironment that sustains and controls the hematopoietic stem cells -- the cells that produce the cells of the blood and the immune system. Protecting this microenvironment, or niche, has thus emerged as a new route for the treatment of these diseases, for which there is currently no fully effective treatment.

"In normal conditions, the microenvironment is able to control the proliferation, differentiation and migration of the hematopoietic stem cell. A specific genetic mutation in these cells results in inflammatory injury to the microenvironment and this control breaks down. What our work shows is that this damage can be prevented or reversed by treatments that target the niche," explained Dr. Mndez-Ferrer.

Indeed, the same team of researchers has demonstrated the efficacy of a possible new treatment, which has been patented through the CNIC. The treatment involves an innovative use of clinically approved treatments for other diseases, so that, according to the authors, "it shouldn't be associated with adverse side effects." The new treatment route has been tested in animals and has received financial backing for a multicenter phase II clinical trial. "This study has a very strong translational and clinical potential," emphasized study first author Dr. Lorena Arranz, who added that "current treatment for myeloproliferative neoplasias is largely symptomatic and directed at preventing thrombosis and fatal cardiovascular events."

The only real cure available today is a bone marrow transplant, which is not advisable in patients over 50 years old. "This makes it important to identify new therapeutic targets for the development of effective treatments," the investigators conclude.

Story Source:

The above story is based on materials provided by Centro Nacional de Investigaciones Cardiovasculares. Note: Materials may be edited for content and length.

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Microenvironment of hematopoietic stem cells can be a target for myeloproliferative disorders

Pushing cells towards a higher pluripotency state

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Stem cells have the unique ability to become any type of cell in the body. Given this, the possibility that they can be cultured and engineered in the laboratory makes them an attractive option for regenerative medicine. However, some conditions that are commonly used for culturing human stem cells have the potential to introduce contaminants, thus rendering the cells unusable for clinical use. These conditions cannot be avoided, however, as they help maintain the pluripotency of the stem cells.

In a study published in Scientific Reports, a group from the RIKEN Center for Life Science Technologies in Japan has gained new insight into the role of CCL2, a chemokine known to be involved in the immune response, in the enhancement of stem cell pluripotency. In the study, the researchers replaced basic fibroblast growth factor (bFGF), a critical component of human stem cell culture, with CCL2 and studied its effect. The work showed that CCL2 used as a replacement for bFGF activated the JAK/STAT pathway, which is known to be involved in the immune response and maintenance of mouse pluripotent stem cells. In addition, the cells cultured with CCL2 demonstrated a higher tendency of colony attachment, high efficiency of cellular differentiation, and hints of X chromosome reactivation in female cells, all markers of pluripotency.

To understand the global effects of CCL2, the researchers compared the transcriptome of stem cells cultured with CCL2 and those with bFGF. They found that stem cells cultured with CCL2 had higher expression of genes related to the hypoxic response, such as HIF2A (EPAS1). The study opens up avenues for further exploring the relationship between cellular stress, such as hypoxia, and the enhancement of pluripotency in cells. Yuki Hasegawa of CLST, who led the study, says, "Among the differentially expressed genes, we found out that the most significantly differentially expressed ones were those related to hypoxic responses, and hypoxia is known to be important in the progression of tumors and the maintenance of pluripotency. These results could potentially contribute to greater consistency of human induced pluripotent stem cells (iPSCs), which are important both for regenerative medicine and for research into diseases processes."

As a way to apply CCL2 towards the culturing of human iPSCs with more consistent quality, the researchers developed dishes coated with CCL2 and LIF protein beads. This allowed stem cells to be cultured in a feeder-free condition, preventing the risk that viruses or other contaminants could be transmitted to the stem cells. While the exact mechanisms of how CCL2 enhances pluripotency has yet to be elucidated, this work highlights the usefulness of CCL2 in stem cell culture.

Explore further: Soft substrates may promote the production of induced pluripotent stem cells

Journal reference: Scientific Reports

Provided by RIKEN

A protein that helps maintain mouse stem cell pluripotency has been identified by researchers at the RIKEN Omics Science Center. The finding, published in the August issue of Stem Cells (first published online ...

Converting adult cells into stem cells that can develop into other types of specialized cells is one of the most active areas of medical research, holding great promise for the treatment of disease and repair ...

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Pushing cells towards a higher pluripotency state

Edmond Woman With MS Undergoes Stem Cell Treatment

EDMOND, Oklahoma -

A former Edmond school teacher battling Multiple Sclerosis went to Chicago for a life-saving stem cell transplant. She's back in town now with her results.

Pamela Gooch says she's the first person with Progressive Relapsing MS to have this particular procedure done. And since the transplant, she's never felt better.

"That just terrible tiredness is gone," said Pamela.

Back to her old, playful self, Pamela says her recent stem cell transplant has given her a new life.

"I can take a nap when I tire and I feel rested, however before, I couldn't get out of bed," Pamela said.

For two years since her MS diagnosis, Pamela always felt drained as her immune system was attacking itself. She even chopped off all her hair before chemotherapy beat her to it.

5/3/2014 Related Story: OK Woman Shaves Head To Prepare For MS Treatment

And in a 20 minute operation only offered in Chicago, she got new stem cells placed in her body. It was a success, until she got a letter from her insurance company backing out of covering the $150,000 procedure and instead opting to pay only a 1/10 of it.

"Pay for the rest of our lives for it, this is what we're going to do."

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Edmond Woman With MS Undergoes Stem Cell Treatment

Stem cell treatment used on horses could help human athletes

The UK Stem Cell Foundation is funding the first ever human study which will involve 10 patients.

It is hoped that this could lead to access to a new treatment within three to five years.

Stem cells will be removed from each patient, expanded in the laboratory, then implanted onto the damaged tendon.

Andy Goldberg, Consultant Orthopaedic Surgeon at the Royal National Orthopaedic Hospital, who will lead the study, said: "There is a real need for effective, non-surgical treatments for Achilles Tendinopathy.

"We have seen stem cell treatments produce impressive outcomes in race horses and this trial will be the first step towards seeing if this is also a viable treatment in humans.

"If things go well, we are hopeful this treatment could have a life-changing impact on patients."

Sir Richard Sykes, Chairman of the UK Stem Cell Foundation, added: "The UK Stem Cell Foundation is delighted to support this first-in-man study.

"Our mission is to help address the critical gap in funding that is hindering the progress of promising stem cell research into new treatments.

"The Autologous Stem Cells in Achilles Tendinopathy study (ASCAT) is an exciting example of taking preclinical work in a natural animal disease model and translating it for human benefit".

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Stem cell treatment used on horses could help human athletes

Stem cell-stimulating therapy saves heart attack patients

PUBLIC RELEASE DATE:

9-Jun-2014

Contact: Kimberly Brown kbrown@snmmi.org 703-652-6773 Society of Nuclear Medicine

St. Louis, Mo. (June 9, 2014) Researchers at the Society of Nuclear Medicine and Molecular Imaging's 2014 Annual Meeting revealed how a protein encourages the production of stem cells that regenerate damaged tissues of the heart following an acute attack (myocardial infarction). They further assert that it has a better chance of working if provided early in treatment. This was confirmed by molecular imaging, which captured patients' improved heart health after therapy.

If given after a heart attack, granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow stem cells that turn down the collateral damage of cell death that occurs after acute myocardial infarction. Other research has shown G-CSF having a beneficial impact on left ventricle ejection fraction, a measurement of how powerfully the heart is pumping oxygenated blood back into the aorta and the rest of the body with each beat. The objective of this study was to find out how beneficial the stem cellstimulating therapy would be if administered early during standard treatment. Early prescription of G-CSF happens to strengthen its effect immediately and after follow up.

"Previous studies have shown that giving G-CSF to unselected heart attack patients failed to satisfactorily improve their condition, but G-CSF may potentially be beneficial if given earlier than 37 hours following myocardial infarction and coronary intervention," remarked Takuji Toyama, MD, the study's principal researcher from the division of cardiology at Gunma Prefectural Cardiovascular Center in Maebashi, Japan. "This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice."

For this study, 40 consecutive patients with acute myocardial infarction were given either G-CSF therapy or saline intravenously for a total of five days beginning during a selected minimally invasive treatment, otherwise known as percutaneous cardiac intervention. Results of one year's worth of SPECT stress tests nailed how earlier start of G-CSF therapy in heart attack patients improves blood flow, access to essential energy and overall cardiac function.

Coronary heart disease caused one out of every six fatalities in the U.S. in 2010, according to 2014 statistics from the American Heart Association. An estimated 620,000 Americans suffered a first heart attack, and 295,000 had a recurrent episode. Collectively, heart attacks occur about once every 34 seconds. Coronary events cause about 379,559 deaths each year.

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Scientific Paper 239: Takuji Toyama, Hiroshi Hoshizaki, Hakuken Kan, Ren Kawaguchi, Hitoshi Adachi, Shigeru Ohsima, Division of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi, Japan; Masahiko Kurabayashi, Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan, "Is the granulocyte colony-stimulating factor therapy in the earliest phase effective to rescue patients with acute myocardial infarction?" SNMMI's 61th Annual Meeting, June 7, 2014, St. Louis, Missouri.

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Stem cell-stimulating therapy saves heart attack patients