January 31, 2012 by

Fat Stem Cells Turn to Muscle: A Treatment for Muscular Dystrophy?

New research published in the journal Biomaterials by University of California, San Diego researcher Adam Engler suggests fat-derived stem cells that are developed on a stiff surface transform into mature muscle cells. This remarkable discovery could lead to new treatments for muscular dystrophy in the future.

Fat stem cells and bone marrow stem cells were grown on surfaces with different degrees of hardness ranging from very hard bone-like surfaces to very soft brain tissue-like surfaces.

The researchers found that the fat derived stem cells were much more likely (up to fifty times) to exhibit proteins that are essential to the cells becoming muscle tissue.
Yuk Suk Choi, a post-doc team member, says that the fat-derived stem cells seem to proliferate better than bone marrow cells when introduced to the hard surfaces. “They are actively feeling their environment soon, which allows them to interpret the signals from the interaction of cell and environment that guide development,” explained Choi.

Unlike bone marrow stem cells, stem cells from fat fused together to form myotubes. Although this phenomenon has been observed in the past, it has never been observed at such a high degree by Engler in the lab. Myotubes comprise an essential step in muscle formation.

Next, Engler and his team plan to observe how fused cells from fat perform in lab mice which are afflicted with a particular form of muscular dystrophy.

However, Dr. Engler cautioned, “From the perspective of translating this into a clinically viable therapy, we want to know what components of the environment provide the most important cues for these cells.”

Filed Under: Adult Stem Cells, Muscular Dystrophy, News, Stem Cell Research Tagged With: , , , , ,
January 30, 2012 by

Medistem Begins Phase II Clinical Trial for Heart Failure

Medistem Inc announced today treatment of 3 heart failure patients in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The trial is aimed at assessing safety and efficacy of the company’s Endometrial Regenerative Cell (ERC) stem cell product in 60 heart failure patients who have no available treatment options. The cells were discovered by Dr. Neil Riordan and the team at Medistem. The “Universal Donor” adult stem cells will be administered using a novel catheter-based retrograde administration methodology that directly implants cells in a simple, 30 minute, procedure.

“We are honored to have had the opportunity to present at the prestigious Cardiovascular Stem Cell Research Symposium, alongside companies such as Athersys, Aastrom, Pluristem, Cardio3, Cytori, and Mesoblast,” stated Thomas Ichim, CEO of Medistem. “The RECOVER-ERC trial is the first trial combining a novel stem cell, with a novel administration procedure. Today cardiac administration of stem cells is relatively invasive and can only be performed at specialized institutions, we feel the retrograde procedure will circumvent this hurdle.”

Medistem has been focusing on the endometrium because this is a unique tissue in that it undergoes approximately 500 cycles of highly vascularized tissue growth and regression within a tightly controlled manner in the lifetime of the average female. One of the first series of data describing stem cells in the endometrium came from Prianishnikov in 1978 who reported that three types of stem cells exist: estradiol-sensitive cells, estradiol- and progesterone-sensitive cells and progesterone-sensitive cells.

Interestingly, a study in 1982 demonstrated that cells in the endometrium destined to generate the decidual portion of the placenta are bone marrow derived, which prompted the speculation of a stem cell like cell in the endometrium. Further hinting at the possibility of stem cells in the endometrium were studies demonstrating expression of telomerase in endometrial tissue collected during the proliferative phase. One of the first reports of cloned stem cells from the endometrium was by Gargett’s group who identified clonogenic cells capable of generating stromal and epithelial cell colonies, however no differentiation into other tissues was reported. The phenotype of these cells was found to be CD90 positive and CD146 positive. The cells isolated by this group appear to be related to maintaining structural aspects of the endometrium but to date have not demonstrated therapeutic potential. In 2007, Meng et al, used the process of cloning rapidly proliferating adherence cells derived from menstrual blood and generated a homogenous cell population expressing CD9, CD29, CD41a, CD44, CD59, CD73, CD90, and CD105 and lacking CD14, CD34, CD45 and STRO-1 expression. Shortly after, Patel’s group reported a population of cells isolated using c-kit selection of menstrual blood mononuclear cells. The cells had a similar phenotype, proliferative capacity, and ability to be expanded for over 68 doublings without induction of karyotypic abnormalities. Interestingly both groups found expression of the pluripotency gene OCT-4 but not NANOG. More recent investigations have confirmed these initial findings. For example, Park et al demonstrated that endometrial cells are significantly more potent originating sources for dedifferentiation into inducible pluripotent cells as compared to other cell populations. Specifically, human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. Additionally, the reprogramming resulted in an average colony-forming iPS efficiency of 0.49 ± 0.10%, with a range from 0.31-0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 ± 0.00% per transduction, with a range from 0.02-0.03%. Suggesting pluripotency within the endometrium compartment, another study demonstrated that purification of side population (eg rhodamine effluxing) cells from the endometrium results in a population of cells expressing transdifferentiation potential with a genetic signature similar to other types of somatic stem cells.

Given the possibility of ERC playing a key role in angiogenesis, Murphy et al utilized an aggressive hindlimb ischemia model combined with nerve excision in order to generate a model of limb ischemia resulting in limb loss. ERC administration was capable of reducing limb loss in all treated animals, whereas control animals suffered necrosis. In the same study, ERC were demonstrated to inhibit ongoing mixed lymphocyte reaction, stimulate production of the anti-inflammatory cytokine IL-4 and inhibit production of IFN-g and TNF-alpha. It is important to note that the animal model involved administration of human ERC into immunocompetent BALB/c mice. The relationship between angiogenesis and post myocardial infarct healing is well-known. Given previous work by Umezawa’s group demonstrating myocytic differentiation of ERC-like cells, administration of ERC into a model of post infarct cardiac injury was performed. Recovery was compared to bone marrow MSC. A superior rate of post-infarct recovery of ejection fraction, as well as reduction in fibrosis was observed with the ERC-like cells. Furthermore, it was demonstrated that the cells were capable of functionally integrating with existing cardiomyocytes and exerted effects through direct differentiation. The investigators also demonstrated in vitro generation of cardiomyocyte cells that had functional properties.

The RECOVER-ERC TRIAL that has begun will recruit 60 patients with congestive heart failure, which will be randomized into 3 groups of 20 patients each. Group 1 will receive 50 million ERC, Group 2 will receive 100 million and Group 3 will receive 200 million. Cells will be administered via catheter-based retrograde administration into the coronary sinus, a 30 minute procedure developed by Dr. Amit Patel’s Team. Each group will comprise of 15 patients receiving cells and 5 patients receiving placebo. Efficacy endpoints include ECHO and MRI analysis, which will be conducted at 6 months after treatment. The trial design is similar to the recent Mesoblast Phase II cardiac study, in order to enable comparison of efficacy.

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , , , ,
January 18, 2012 by

Umbilical cord stem cells may lead to new spinal cord injury and multiple sclerosis treatments

Researchers in Florida have accomplished converting umbilical cord stem cells into other cell types. According to University of Central Florida bioengineer James Hickman, it’s the first time that non-embryonic cells have accomplished this feat. His research group published this work in the January 18th issue of ACS Chemical Neuroscience.

Two major benefits of umbilical cord-derived stem cells are that they have not been shown to cause adverse immune system reactions and they pose no ethical issues since they come from a source that would be naturally discarded anyway.

Hedvika Davis, a post-doc researcher and lead author of the paper, had to search for the right chemical to coax the stem cells into becoming oligodendrocytes, which are cells that insulate nerves residing in the brain and spinal cord.

Other researchers had already shown that oligodendrocytes bind with a hormone called norepinephrine and Davis theorized that this could be the key. So she used norepinephrine and other growth factors to induce the cells to differentiate into oligodendrocytes. The only problem was that the cells were not sufficiently developed as they would be in the body.

So Davis devised a novel approach of approximating the body’s environment in the lab. By growing the cells on top of a slide, with another slide on top, Davis was able to simulate a 3-dimensional environment and grow mature oligodendrocytes.

Because oligodendrocytes produce myelin, researcher believe that this discovery might lead to treatments for multiple sclerosis, spinal cord injury and diabetic neuropathy.

Filed Under: Adult Stem Cells, Cord Blood Stem Cells, Multiple Sclerosis, News, Spinal Cord Injury, Stem Cell Research Tagged With: , , , , , ,
December 6, 2011 by

Stem Cell Treatments for Pemphygoid: Jane Wrede

“With such strong signs of remission and impatience with side effects, I took it upon myself to taper prednisone from 20 to 7.5mg/day and after 3 weeks at 7.5, I see no change in my healthy oral condition. All sores healed and no new blisters. I count this as successful!”

My name is Jane Wrede I have an autoimmune disease called Pemphygoid. Pemphygoid symptoms in my mouth and throat gradually improved after stem cell treatment so that my gums are firm, I feel no pain and can eat all but hot and spicy food! My eyes continue to be dry and I use sterile drops when they feel tired and sore. This is less severe than before and not until late in the day and sometimes at night. With such strong signs of remission and impatience with side effects, I took it upon myself to taper prednisone from 20 to 7.5mg/day and after 3 weeks at 7.5, I see no change in my healthy oral condition. All sores healed and not new blisters. I count this as successful!

Jane Wrede

Filed Under: Autoimmune Diseases, Patient Stories, Pemphygoid Tagged With: , , , , , ,
December 6, 2011 by

Stem cell therapy for juvenile dermatomyositis: Nathan Byrd

“Nathan, my son, is only on Prednisone at 3 mg q d now. Absolutely no problems at all. No weakness. No pain. No stiffness. Rash is gone. The calcinosis is less based on a recent x-ray. Flow cytometry was normal.

“(Nathan has) Absolutely no problems at all. No weakness. No pain. No stiffness. Rash is gone.”

How can I ever express my gratitude to all of you?”

– Richard W Byrd MD

Filed Under: Autoimmune Diseases, juvenile dermatomyositis, Patient Stories Tagged With: , , , ,
April 29, 2011 by

Stem Cell trial volunteers thank doctors at reunion lunch

Miami Herald, by Fred Tasker, ftasker@MiamiHerald.com
Stem cell therapy was originally used for the treatment of leukemias in the form of bone marrow transplant. Nearly 2 decades after this groundbreaking work, clinical trials initiated using bone marrow stem cells for treatment of heart patients. Bone marrow stem cells possess the ability to stimulate new blood vessel formation, a process called angiogenesis, which is essential in: a) accelerating healing after a heart attack; and b) in patients who have angina, stimulating new blood vessels to grow and take over the function of the clogged arteries that are causing the angina.
Initial work in this area involved administering stem cells from the bone marrow that were non-purified, directly into the heart muscle. Subsequently new techniques were developed so that open heart surgery was not needed. These techniques include the use of catheter-based delivery systems. Additionally, scientists found that one type of stem cell that is found in the bone marrow, called the mesenchymal stem cells, is actually more potent than bone marrow non-purified cells. Clinical trials have been performed with mesenchymal stem cells for heart failure. One of the major ones involved intravenous administration of “universal donor” cells. This article describes some of the patients that participated in Osiris’ 51 patient clinical trial.
“I believe in miracles, God — and my doctors,” said Edgar Irastorza, 33, the youngest of 51 patients at the luncheon.
Early results are promising, says Hare, director of UM’s Interdisciplinary Stem Cell Institute.
“We don’t know what the results will be, but things are going well. The fact that you’re here is testament to that,” he told the patients, united for the first time at a luncheon titled “Heart of a Pioneer” to celebrate their struggle.
Irastorza, a Miami property manager, said he died briefly on Oct. 6, 2008. A genetic defect gave him such a serious heart attack that his heart stopped for a few minutes. Doctors who revived him said half his heart was dead and warned him to prepare for a short, disabled life. They wanted to insert a defibrillator into his chest.
“I didn’t want that,” he said. “I didn’t want to give up sex and dancing.”
On March 3, 2010, UM doctors used a catheter inserted through a slit in his groin to inject millions of tiny stem cells into his damaged heart.
At the Friday luncheon, Irastorza presented to the crowd a five-minute video of his new self, doing an energetic, head-spinning break dance.
“I’m not completely back to normal, but, compared to before, it’s night and day,” he said.

Felix Morales, 80, a retired agriculture worker, had a heart attack 25 years ago and recently had become too easily fatigued to take care of the collards and peppers and the mamey and mango trees in his Miami backyard.
A year ago, he got one of the stem-cell treatments. “It took a while, but I feel good right now,” he said. “I have no words to express my gratitude.”
Evangeline Gordon, 40, a state probation officer from Miami, called 911 one October night in 2009, thinking she had a bad gas attack. To her shock, doctors told her a heart attack had damaged 70 percent of her heart muscle. They began discussing a heart transplant.
Instead, she volunteered for the UM program and got stem cells from a donor. Like most of the others, she doesn’t know if she got real stem cells or a placebo treatment used for comparison.
“I’m up and down,” she said Friday. “I still get angina and fatigue, but I don’t feel like I’m going down anymore.”

Filed Under: Clinical Trials, News, Stem Cell Research, Stem Cell Therapy Tagged With: , , , , , ,
February 20, 2011 by

Stem Cells Help Women Regrow Breasts After A Mastectomy

By Lucy Johnston

Express News

Scientists in the UK and Australia have been implementing a new technique to benefit women who have had a mastectomy to remove cancerous cells. The technique involves placing a special plastic mould under the skin and then injecting the area with the patient’s own stem cells. The cells are cultured from adipose tissue that is removed from the patient by liposuction. The stem cells are removed from the fat tissue and grown to a larger number, then recombined with the fat and injected back into the body. Results generally take from six months to a year, over which the fat and stem cells grow slowly until new breast tissue is formed. Since the tissue is grown by the patients’ own body, the breasts look and feel natural and are much more comfortable than silicone implants.

The treatment was discovered by observing the way the body reacts to wounds. “Nature doesn’t like a vacuum,” said Professor Wayne Morrison of Melbourne University, who has performed the procedure himself, “so the chamber itself, because it is empty, tends to be filled in by the fat. We observed this and decided it could be used to help treat women who’d lost their breasts to ­cancer. Fat cells can grow to fill a void in the same way that the body repairs tissue damage. Our research shows fat ­continued to grow until it had filled the area where there had once been a ­natural breast. We attach the area to a blood supply from the chest or under the arm which helps the fat grow. The mould used by surgeons helps create a breast shape in which the fat forms.”

The current treatment for mastectomy patients involves taking tissue from the buttock to form a new breast. The results of this treatment are variable, however, and the implementation of the use of stem cells will hopefully improve the outlooks for women. The treatment could also have potential for cosmetic surgeries as well, possibly replacing saline or silicone implants, which have been associated with various side effects.
Professor Morrison said: “We hope the technology will have a significant impact around the world. There are a lot of women who don’t have ­reconstructive surgery for whatever reason or have silicone breast implants but this will give them their own tissue back.”

The patients that have been treated so far have had very impressive results, according to Professor Kefah Mokbel, consultant breast surgeon at St. George’s Hospital, London. The plastic scaffolding used as a mould must be removed surgically, however the procedure is minimally invasive. Researchers hope to develop a biodegradable scaffold which will dissolve once the implant has grown. The treatment is also not used on women who have been cancer free for less than a year, in order to prevent the stem cells from causing further tumor growth.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , , ,
December 30, 2009 by

Stem Cells Might Reverse Heart Damage From Chemo

One of the great findings of regenerative medicine was that organs previously believed to be incapable of healing themselves actually contain stem cells that in response to injury cause some degree of healing. The problem being that these "endogenous healing mechanisms" are usually too small to mediate effects that are visible at the clinical level. For example, the brain was considered to have very limited ability to heal itself after damage. Recent studies that have allowed for observation of brain cells after experimental strokes have led to the discovery of brain stem cells in the dendate gyrus and subventricular zones of the brain, stem cells that start to multiple after a stroke. Interestingly, various hormones such as human chonrionic gonadotropin, are capable of stimulating brain stem cell multiplication. This is currently being used in clinical trials for stroke by the company Stem Cell Therapeutics.

In the area of heart failure, it was also believed that once cardiac tissue is damaged, the only repair process that the body performs is production of scar tissue, which is pathological to the patient. While this scar tissue is found in the majority of the injured area, molecular studies have revealed the existence of cardiac specific stem cells, which start to multiply after injury and serve to repair, albeit in small amounts, the infarct area.

One way to augment endogenous repair processes is to administer stem cells from the bone marrow, which are known to produce various growth factors that assist the tissue-specific stem cell in mediating its activity. Another way is to physically extract the tissue specific stem cells, expand them outside of the body and reimplant them into the damaged area.

In a recent publication in the journal Circulation, Piero Anversa, M.D., director, Center for Regenerative Medicine, Departments of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women’s Hospital, Boston and Roberto Bolli, M.D., chief, cardiology, and director, Institute of Molecular Cardiology, University of Louisville, Kentucky, describe the use of cardiac specific stem cells in treatment of animals whose hearts of been damaged by the chemotherapeutic drug doxorubicin.
Doxorubicin is a chemotherapeutic drug that is mainly used in the treatment of breast, ovarian, lung, and thyroid cancers, as well as for neuroblastoma, lymphoma and leukemia. One of the main limiting factors to increasing the dose of doxorubicin to levels that can lead to tumor eradication is that it causes damage to the heart muscle, the myocardium.

In the published study, the investigators expanded the cardiac specific stem cells from rats, gave the rats high doses of doxorubicin and in some rats injected back cardiac specific stem cells, whereas other rats received control cells. The rats that received the cardiac specific stem cells had both preservation of cardiac function, and also regeneration of the damaged heart tissue. This is an important finding since the type of damage that doxorubicin does to the heart is different from other types of heart damage that have been studies, such as the damage that occurs after a heart attack. These data seem to suggest that stem cell therapy may be useful in a variety of injury situations.

"Theoretically, patients could be rescued using their own stem cells," said study author Dr. Piero Anversa, director of the Center for Regenerative Medicine at Brigham and Women’s Hospital in Boston. Dr. Aversa is one of the original discoverers of the cardiac specific stem cell when he published experiments in dogs demonstrating multiplication of cells in the myocardium that seem to have ability to generate new tissue after damage (Linke et al. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71).

"A Phase 1 clinical trial using a similar procedure in people is already under way", said Dr. Roberto Bolli, chief of cardiology and director of the Institute of Molecular Cardiology at the University of Louisville in Kentucky, who is heading the trial. The FDA has approved a Phase I clinical trial using cardiac specific stem cells in 30 patients who have congestive heart failure due to disseminated atherosclerosis. "In the trial, participants’ cardiac tissue will be harvested, the stem cells isolated and then expanded in vitro from about 500 cells to 1 million cells over several weeks", Bolli explained. "Several months after the patient has undergone bypass surgery, the stem cells will be re-injected." A similar clinical trial is being performed at Cedars Sinai in Los Angeles.

While the problems of tissue extraction (which is performed by an invasive procedure requiring biopsy of heart tissue) and cost of expansion are still formidable hurdles to widespread implementation, it is believed that the clinical evidence of a therapeutic response will open the door to other avenues of expanding tissue specific stem cells, such as administration of growth factors that can accomplish this without need for cell extraction outside of the body.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , ,
December 28, 2009 by

Stem Cell as Anti-Aging “Medicine”

Medistem Inc issued a press release describing a collaborative publication between the University of California San Diego, Indiana University, University of Utah, the Dove Clinic for Integrative Medicine, Biotheryx, NovoMedix, The Bio-Communications Research Institute, The Center for Improvement of Human Functioning International and Aidan Products, discussing the contribution of circulating endothelial cells to prevention of aging. The publication also provided data showing that healthy volunteers who have been administered the food supplement Stem-Kine had a doubling of circulating endothelial progenitor cells.

The paper "Circulating endothelial progenitor cells: a new approach to anti-aging medicine?" is freely accessible. "Numerous experiments and clinical trials have been published describing the importance of these repair cells that the body possesses to heal internal organs," stated Dr. Doru Alexandrescu from Georgetown Dermatology, a co-author of the publication. "However, to our knowledge, this is the first comprehensive blueprint in the peer-reviewed literature of how this knowledge may be applied to the question of aging."

The paper summarizes publications describing correlations between decline of circulating endothelial cells and aging/deterioration of several organ systems. The main hypothesis of the publication is that the bone marrow generates a basal number of circulating endothelial cells that serve to continually regenerate the cells that line the blood vessels. Many diseases that are prevalent in aging such as Alzheimer’s are associated with dysfunction of the blood vessel’s ability to respond to various stimuli. This dysfunction is believed to be caused by diminished numbers of circulating endothelial progenitor cells.

Other conditions such as peripheral artery disease are also associated with reduction in this stem cell population, however, when agents are given that increase the numbers of these cells, the degree of atherosclerosis-mediated pathology is decreased. This was demonstrated in a study that administered the drug GM-CSF, which causes an increase in circulating endothelial progenitor cells in a manner similar to Stem-Kine. Unfortunately, drugs currently on the market that have this ability are very expensive and possess the possibility of numerous side effects. The Stem-Kine food supplement is sold as a neutraceutical and is made of natural ingredients that have already been in the food supply.

Another interesting point made by the paper was that the body modulates the number of circulating endothelial progenitor cells based on need. In stroke, the number of circulating endothelial progenitor cells markedly increases in response to the brain damage. Patients in which a higher increase is observed are noted to have a higher chance of recovery. Therapeutic interventions that contain endothelial progenitor cells such as administration of bone marrow cells after a heart attack, are believed to work, at least in part, through providing a cellular basis for creation of new blood vessels, a process called angiogenesis.

Patients with inflammatory conditions ranging from chronic heart failure, to type 2 diabetes, to Crohn’s disease are noted to have a reduction in these cells. The reduction seems to be mediated by the inflammatory signal TNF-alpha. Studies reviewed in the paper describe how administration of antibodies to TNF-alpha in patients with inflammatory conditions results in a restoration of circulating endothelial progenitor cells.

In addition to the possible use of Stem-Kine for restoration/maintenance of circulating endothelial progenitor cells, the publication discusses the possibility of using such cells from sources outside of the body, for example cord blood. Although it was previously thought that cord blood can be used only after strict HLA matching, recent work supports the idea that for regenerative medicine uses, in which prior destruction of the recipient immune system is not required, cord blood may be used without immune suppression or strict tissue matching. This is discussed in the following paper: Cord blood in regenerative medicine: do we need immune
suppression?.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
December 23, 2009 by

Adenosine inhibits chemotaxis and induces hepatocyte-specific genes in bone marrow mesenchymal stem cells

Bone marrow cells contain several populations that are useful for regenerating injured/aged tissue. These cells include hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and some argue, progenitor cells left over from embryonic periods that are still capable of differentiating into numerous injured tissue. It has been known for some time that bone marrow cells are capable of treating liver failure both in vitro and in early clinical trials, as can be seen on this video: Stem Cell Therapy for Liver Failure. Other types of stem cells useful for treatment of liver failure, such as cord blood stem cells, may be seen on this video: Cord Blood and Bone Marrow Stem Cells for Liver Failure.

One of the major questions with adult stem cell therapy is how do the stem cells go to where they are needed? Some people have made the argument that stem cells administered intravenously do not cause systemic effect because the majority get stuck in the lung and liver. Although cell sequestration is an issue, numerous studies have demonstrated therapeutic effects after intravenous administration of stem cells. Perhaps the most well-known stem cell homing molecule is stromal derived factor (SDF-1), which is made by injured and/or hypoxic tissue and causes stem cell mobilization and migration through activation of the CXCR4 receptor. The SDF-1/CXCR4 axis has been found in numerous conditions of tissue injury such as: stroke, heart attack, acoustic injured ear, liver failure, and post-transplant reconstitution of bone marrow. To understand how this “chemokine” works, the following video will describe it as relevant to stem cell repopulation post-irradiation: Homing of Stem Cells to Target Tissue

In a study published today scientists examined another signal made by injured tissue in order to assess whether it may act like SDF-1 and “call in” stem cells. The signal chosen was the amino acid adenosine, which is released from injured/necrotic cells. They found that adenosine did not by itself induce chemotaxis of mesenchymal stem cells (MSC) but dramatically inhibited MSC chemotaxis in response to the chemoattractant hepatocyte growth factor (HGF). Inhibition of HGF-induced chemotaxis by adenosine requires the A2a receptor and is mediated via up-regulation of the cyclic adenosine monophosphate (AMP)/protein kinase A pathway. Additionally, the investigators found that adenosine induces the expression of some key endodermal and hepatocyte-specific genes in mouse and human MSCs in vitro.

The ability of adenosine to modulate migration/differentiation processes implies that numerous paracrine/autocrine interactions are occurring during tissue injury. It will be critical to identify how to manipulate such factors to obtain maximal therapeutic responses.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
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