Trish Stressman and her husband Scott discuss how stem cell therapy at the Stem Cell Institute in Panama allowed her to recover to the point at which she could safely give birth and care for her newborn daughter, Savannah Hope.
Prior to stem cell treatment, Trish had no core muscles and would not have been able to even safely hold a baby, let alone care for one. Since stem cells, that’s all changed. Congratulations Trish, Scott and Savannah Hope!
November 29, 2012 by
Giving birth after stem cell treatments for spinal cord injury
August 28, 2012 by
Blood Stem Cells Permanently Damaged by Alcohol
Bone marrow stem cells are extremely sensitive to the primary by-product of alcohol, which causes permanent damage to their DNA claims researchers from the Medical Research Council (MRC) Lab of Molecular Biology.
The research, which was conducted on mice, uncovers two mechanisms that normally control this type of damage; a protein group that recognizes and repairs DNA damage and an enzyme that eliminates acetaldehyde, alcohol’s toxic breakdown product.
Mice lacking both protective mechanisms developed bone marrow failure stemming from blood stem cell damage.
These results mark the first time that scientists have been able to explain why bone marrow fails in Fanconi anemia (FA) patients. FA is a rare genetic disorder.
The report concludes that FA turns off the bone marrow’s “repair kit” via FA gene mutation which causers DNA damage from acetaldehyde to continue unchecked. This damage is responsible for bone marrow failure and developmental defects in FA patients and makes them especially vulnerable to blood and other types of cancer.
These findings may have particular significance for the world’s Asian population, many of whom suffer from “Asian flush syndrome”. People with AFS lack the enzyme ALDH2 and therefore could be particularly susceptible to DNA damage. The authors warned that this subset of the Asian population could suffer permanent DNA damage with alcohol consumption and be more highly prone to blood cancer, bone marrow failure and premature aging than the Asian population at-large.
“Blood stem cells are responsible for providing a continuous supply of healthy blood cells throughout our lifespan. With age, these vital stem cells become less effective because of the build up of damaged DNA. Our study identifies a key source of this DNA damage and defines two protective mechanisms that stem cells use to counteract this threat. Last year we published a paper showing that without this two-tier protection, alcohol breakdown products are extremely toxic to the blood. We now identify exactly where this DNA damage is occurring, which is important because it means that alcohol doesn’t just kill off healthy circulating cells, it gradually destroys the blood cell factory. Once these blood stem cells are damaged they may give rise to leukaemias and when they are gone they cannot be replaced, resulting in bone marrow failure,” Dr KJ Patel, who is the primary investigator.
“The findings may be particularly significant for a vast number of people from Asian countries such as China, where up to a third of the population are deficient in the ALDH2 enzyme. Alcohol consumption in these individuals could overload their FA DNA repair kit causing irreversible damage to their blood stem cells. The long-term consequences of this could be bone marrow dysfunction and the emergence of blood cancers,” Patel added.
“This study provides much sought-after explanation of the biology underpinning the devastating childhood disease Fanconi anemia. In future this work may underpin new treatments for this genetic disease, which currently is associated with a very poor prognosis. It also helps to inform large numbers of the global population, who are deficient in the ALDH2 enzyme, that drinking alcohol may be inflicting invisible damage on their DNA,” commented Sir Hugh Pelham, director of the MRC Laboratory of Molecular Biology.
February 3, 2012 by
Inhaling Stem Cells for Treating Parkinson’s
Danielyan et al. Rejuvenation Res.
Stem cells have been delivered in a variety of ways: intravenously, into the spinal canal (intrathecally), into the brain (stereotactically), into the joint (intra-articularly), and into the cardiac muscle (endocardially). Scientists from the Department of Clinical Pharmacology, University Hospital of Tübingen , Tübingen, Germany have reported today a new way of delivering stem cells: via the nose.
Previous experiments administering stem cells for the treatment of Parkinson’s were primarily aimed at injection directly into the brain using sterotactic methods. These methods are highly invasive and there is always the potential of causing injury. Additionally some groups have used intravenous administration but the washout and number of cells being stuck in the lung and liver was reported as a potential problem.
The promise of using stem cells for the treatment of Parkinson’s comes not only from the direct regenerative ability of stem cells such as mesenchymal stem cells, but also from the fact that Parkinson’s is associated with inflammatory cytokine production, which has been previously demonstrated to be inhibited by stem cell administration.
Intranasal administration of bone marrow mesenchymal stem cells was performed in rats induced to develop a Parkinson’s like disease in which the dopaminergic cells were killed by administration of the toxin 6-hydroxydopamine (6-OHDA).
In rats that received the stem cells intranasally it was possible to find stem cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10(6) MSCs applied intranasally, 24% of the stem cells could be detected for least 4.5 months in the brains of 6-OHDA rats. It appears that the stem cells administered actually could proliferate in vivo as shown by expression of proliferating cell nuclear antigen on the administered mesenchymal stem cells.
Functionally it appeared that the intranasal administration increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase apoptotic cells as detected by TUNEL. Decreases in dopamine were prevented by cellular administration. A decrease in the inflammatory cytokines TNF, IFN-g, IL-2, 2, 6, and 12 was observed to be associated with the administration of cell therapy.
It will be interesting to see if this easy to apply technique will enter clinical trials. Already clinical trials are using non-conventional means of stem cell administration, for example the topical application of stem cells for burn wounds, which is being performed by Dr. Amit Patel from the University of Utah, who we interviewed for the Cellmedicine news blog above.
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.”
May 23, 2011 by
Bone Marrow Stem Cells Successful For Liver Failure Caused by Hepatitis B
Peng et al. Hepatology.
The liver is the most regenerative solid organ in the body. One can resect 2/3 of the liver and it will still regenerate back to normal size. There have been several experimental studies in animals where induction of liver injury is treated by administration of bone marrow stem cells. A video describing this may be seen at this link http://www.youtube.com/watch?v=XGdehdRApb0. Previous use of bone marrow cells in patients with liver failure has been described in a Japanese publication that is presented in this video http://www.youtube.com/watch?v=DdH6Mm4w98I.
A recent study Peng et al. Autologous bone mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short-term and long-term outcomes. Hepatology. 2011 May 23 from the 3rd Affiliated Hospital of Sun Yat-sen University, in GuangZhou, China reported outcomes of 53 patients with hepatitis B induced liver failure treated with 120 ml of their own bone marrow stem cells infused via the hepatic artery. These patients were compared to 105 control patients that were matched for age, gender, and liver enzymes. Additionally, the functional index of liver failure, the Model for End-Stage Liver Disease (MELD) score, was matched between the treated and control groups.
Bone marrow stem cells were isolated without complications. The cells were administered as a slow infusion into the hepatic artery. Given that hepatitis is associated with an increase in hepatic cancer, one of the concerns of bone marrow stem cell administration into this patient population is the theoretical possibility of accelerating tumor formation. This appeared not to be the case. Specificallyt, follow-up at 192 weeks post treatment revealed no differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group. In terms of efficacy, it appeared that 2 to 3 weeks after administration of bone marrow stem cells, the levels of ALB, TBIL, PT and the MELD score of patients who received stem cells were significantly improved as compared to control patients. Improvements where maintained in the majority of patients.
These data support the possibility of using autologous stem cells in the treatment of liver failure. One possible new and less invasive method would be to mobilize the existing stem cells of the patient by administering drugs such as G-CSF (Neupogen) that trigger entry of bone marrow stem cells into circulation. The therapeutic activity of stem cell mobilization was demonstrated by Zhang et al. Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with d-galactosamine-induced acute liver failure. Toxicol Lett. 2011 Apr 27 who demonstrated that 5 day administration of G-CSF had therapeutic effects in the d-galactosamine-stimulated liver failure model.
February 6, 2011 by
UW Researchers Make Stem Cell Breakthrough
Seung Park, Badger Herald
Researchers at the University of Wisconsin have made a breakthrough in stem cell research. Igor Slukvin headed the team that has successfully reprogrammed bone marrow cells into induced pluripotent stem cells (iPSCs). “This is important because blood banks have huge amounts of samples of bone marrow,” he said. “You can select as many types of cells as you want and make stem cells out of them.”
This regression was a major accomplishment, as reprogramming a cell is similar to an adult human reversing development and becoming a child again, according to Timothy Kamp, an associate professor of medicine. “When our organs develop, it’s a one-way street as you go from a precursor stem cell which grows and forms specialized tissues for various systems,” Kamp said. “As these cells grow progressively more specialized, they can’t go back and return to being a stem cell.” Obviously, this problem has been overcome, the concept behind the reprogramming comes from a set of DNA binding proteins that regulate gene expression.
Slukvin also took cells from a patient with chronic myeloid leukemia and generated transgene-free iPSCs from their bone marrow. These cells show a unique translocation of a chromosome while also maintaining the pluripotency of an embryonic stem cell. The implication of this being that the disease can now be followed, as they have regressed back into stem cells, the redevelopment of the disease will be able to be observed.
February 2, 2011 by
Injured Liver Calls in Bone Marrow For Help?
Li et al. Cells Tissues Organs
It is known that administration of bone marrow cells into patients with liver failure has the ability to improve enzyme function and overall health http://www.youtube.com/watch?v=DdH6Mm4w98I. Additionally, numerous animal models have demonstrated that injection of various types of stem cells can result in regeneration of injured liver tissue. For example, Manuelpillai et al demonstrated that injection of human mesenchymal stem cells derived from the amnionic membrane into immune competent mice whose livers were damaged by carbon tetrachloride results in reduction in liver injury http://www.ncbi.nlm.nih.gov/pubmed/20447339. Even more interesting, administration of compounds that “instruct” bone marrow cells to enter circulation such as G-CSF, have been demonstrated to improve liver function and actually prevent mortality after liver injury http://www.ncbi.nlm.nih.gov/pubmed/20881764. This is relevant because G-CSF is a medication that is FDA approved and possesses a favorable safety profile.
One of the main scientific questions in the area of liver failure is whether the liver is actually “calling in” bone marrow stem cells to try to heal it after liver damage, or whether the therapeutic effects of stem cells in liver failure are an epiphenomena. In situations of cardiac damage after an acute myocardial infarction it has been demonstrated that the injured tissue causes upregulation of the protein SDF-1, which recruits bone marrow stem cells into the heart in order to promote healing. Whether similar mechanisms are at play in liver injury is not known. Part of the puzzle has to do with the fact that liver injury is a more chronic process than heart attacks and therefore recruitment of stem cells may be occurring at a much lower level. Alternatively, it is also known that chronic inflammatory processes actually suppress stem cell activity. So it may be that in chronic liver failure the stem cells are actually inhibited from possessing regenerative function.
This question was addressed in a recent study in which the gene expression profile of bone marrow cells was examined in animals with liver failure induced by administration of the hepatotoxin D-galactosamine to rats. To assess gene expression the Affymetrix GeneChip Rat Genome 230 2.0 Array was used, which quantifies gene expression of every gene in the rat genome. The scientists found that more than 87.7% of the genes/probe sets that were upregulated more than 2-fold in the bone marrow cells of rats with liver failure were also expressed by the liver cells, including 12 genes involved in liver development, early hepatocyte differentiation and hepatocyte metabolism. The concurrent upregulation of these genes was verified by the technique of reverse transcriptase polymerase chain reaction (RT-PCR).
The scientists also found that 940 genes were expressed in both the bone marrow cells of rats with liver failure and the hepatocytes of rats with liver failure but not in control cells. Specifically, many of the genes that were uprgulated in both the bone marrow and the liver seemed to be involved in regeneration of damaged tissue.
These data support the concept that the bone marrow stem cells can respond in similar ways to liver cells to injury. The hypothesis has been proposed by the authors that the bone marrow acts as a reservoir for the stem cells that are capable of regenerating liver. The mass amount of data in this publication is very interesting and requires detailed analysis to make sense of.
February 1, 2011 by
Limb Transplants Facilitated by Bone Marrow Stem Cells
Kuo et al. Plast Reconstr Surg. 2011 Feb;127(2):569-79.
Composite tissue allografts are usually transplants of anatomical structures that contain multiple types of tissues. We have seen numerous high-profile examples of human composite tissue allografts such as whole hands, faces, and arms. While advancement of surgical techniques have made such transplants a reality, immunologically-mediated rejection remains a formidable problem.
Mesenchymal stem cells are particularly interesting in terms of an “adjuvant” to transplant immune suppression for several reasons.
Firstly, mesenchymal stem cells are known to be immune modulatory. It is known that these cells suppress activation of dendritic cells (which are involved in stimulating immune responses). Mesenchymal stem cells also inhibit CD4 and CD8 T cell responses. This is beneficial in that the CD4 cell coordinates immune attacks and the CD8 T cell causes cytotoxicity of organs that are being rejected. Perhaps even more interestingly, mesenchymal stem cells are known to stimulate production of T regulatory cells. These are cells of the immune system that suppress other immune cells and are associated with prolongation of transplanted graft survival. At a molecular level how the mesenchymal stem cells modulate the immune system seems to involve several biological modulators. Mesenchymal stem cells express the enzyme indomlamine 2,3 deoxygenase, which metabolizes tryptophan. T cells are highly dependent on tryptophan for activation. Mesenchymal stem cells have been demonstrated to actively induce T cell death by localized starvation of tryptophan. Additionally, mesenchymal stem cells produce various immune suppressive cytokines such as Leukemia Inhibitory Factor (LIF), IL-10, TGF-b, and soluble HLA-G. One interesting method by which mesenchymal stem cells suppress the immune system is by expression of surface-bound immune cell killing molecules such as Fas ligand. Evidence supporting the immune suppressive effects of mesenchymal stem cells includes the ability of these cells to control pathological immunity such as graft versus host disease, multiple sclerosis, and Type 1 diabetes.
Secondly, mesenchymal stem cells are known to be angiogenic. This is the process of new blood vessel formation. Subsequent to organ transplantation it is essential that the transplanted organ receive a proper blood supply. While ligation of major blood vessels is performed during the transplantation surgery, proper integration of the donor and recipient blood vessels is an important factor in graft survival.
Thirdly, mesenchymal stem cells have the ability to repair injured organs. There is a substantial amount of injury that occurs as a result of the organ procurement, transportation , and implantation procedure. This injury is termed ischemia/reperfusion injury. The extent of ischemia reperfusion injury contributes more to graft long term survival as compared even to MHC mismatches. As a result of the injury chemoattractants are generated that cause homing of stem cells into the injured organ. It is possible that these stem cells actually contribute to healing and perhaps regeneration of the injured organ.
In the publication discussed, the authors used a porcine model of hind limb transplantation. Four groups of pigs were used:
Group 1: Four untreated recipients
Group 2: Three recipients that received mesenchymal stem cells alone
Group 3: Five recipients that received cyclosporine alone
Group 4: Three recipients that received cyclosporine, irradiation, and mesenchymal stem cells
It was found that treatment with mesenchymal stem cells along with irradiation and cyclosporine A resulted in significant increases in allograft survival as compared with other groups (>120 days; p = 0.018).
Flow cytometric analysis revealed a significant increase in the percentage of CD4/CD25 and CD4/FoxP3 T cells in both the blood and graft in the mesenchymal stem cell/irradiation/cyclosporine A group.
These preliminary data suggest that addition of mesenchymal stem cells to the combination of cyclosporine and irradiation resulted in significant allograft survival. Unfortunately in Group 3 they did not add irradiation so it is impossible to know whether the graft survival was caused by the irradiation or by the mesenchymal stem cells.
Previous collaborations between Thomas Ichim of Medistem and Hao Wang’s group from University of Western Ontario, Canada suggests that a radioresistant element in free bone transplants contributes to prolonged allograft survival. It may be possible that the radioresistant cells were mesenchymal stem cells in nature. This is an area in which future studies are definitely warranted.
January 31, 2011 by
Nine Patients with Crohn’s Disease Treated by Intravenous Administration of Mesenchymal Stem Cells
Marjolijn et al. Gut 59:1662
Mesenchymal stem cells are known to be suppressive to immune cells such as T cells, dendritic cells, and natural killer cells. Studies have demonstrated that patients suffering from the immune disease graft versus host enter remission after administration of donor or third party mesenchymal stem cells. One of the manifestations of graft versus host disease is inflammation of the colon, resembling autoimmune colitis and Crohn’s disease.
Some of the previous studies investigating this condition have demonstrated therapeutic effects of mesenchymal stem cells on colonic inflammation. Given this rationale, a recent paper examined the effects of autologous mesenchymal stem cells in the treatment of Crohn’s disease refractory to steroids, immune suppressants, and biologics.
50-100 ml of bone marrow cells were isolated from family members or third-party donors and expanded in vitro. Cells where grown to administer two doses, a week a part, of 1-2 x 10(6) cells per kg body weight. Patients were treated by intravenous administration and followed up for 6 months.
MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment. Additionally, 3 other patient required surgery, presumably as a result of disease progression.
These data demonstrate that intravenous administration of bone marrow mesenchymal stem cells appears to be safe for treatment of Crohn’s disease, however larger studies are necessary to determine whether statistically significant efficacy exists.
