February 11, 2011 by

Test Tube Meat No Longer Science Fiction, Dutch Researchers Say

Rudy Ruitenberg

The idea of growing meat in a laboratory was developed in 1950, however was not patented until 1999. Due to more recent scientific discoveries, this idea is now becoming a reality. This development may help to ease environmental damage caused by the enormity of the animal farming market. Around 70 percent of farmland is used for the production of meat and livestock industry account for 18 percent of greenhouse-gas emissions.

This project is being led by Henk Haagman at the University of Utrecht, he and his team are using stem cells to grow muscle tissue. The reality of buying lab-grown meat in the supermarket may be a few years away, however this development is the first step in the mass production of engineered meat.

“The project will be a success if in four years time it’s clear under what conditions consumers will eat in-vitro meat,” said Cor van der Weele, a philosopher leading the study of the ethical and social issues of cultured meat. Meat produced in a laboratory is “not a meat replacement, it’s real meat,” Van der Weele said. “I’ve been calling it in-vitro meat recently, that’s the technical name,” Van der Weele said. “Cultured meat isn’t appealing and creates too much of a ‘yuck’ reaction.”

Filed Under: News, Stem Cell Research Tagged With: , , , ,
February 9, 2011 by

Curious? The Science of Skin Care

Caiti Currey

Stem cells have become a highly talked about subject in the treatment of many diseases and health problems, and have now come into the limelight as a possible treatment for skin rejuvenation. Men and women alike are constantly seeking a product that will reduce the signs of aging, and stem cells have now been proven to act as such.

Lilacs are a very popular flower for many reasons, but a new discovery has shown that stem cells in lilac leaves can reduce the signs of aging and rejuvenate the skin. The leaf stem cell is a very effective antioxidant, protecting the skin from the damage that can be caused by free radicals. Stem cells from grapefruits are also known to function as protection from damage. Swiss apple is also known for its ability to preserve, protect and stimulate the growth of human stem cells.

Dr. Jennifer Linder, Chief Officer for PCA SKIN has used these plant stem cells to develop products that have been proven to be beneficial to the skin. The Rejuvenating Serum uses epidermal growth factor technology to stimulate cell and skin renewal.

Filed Under: News, Stem Cell Research Tagged With: , , , ,
February 8, 2011 by

Skin-cell spray gun drastically cuts healing time for burns

In the past, the most common way to treat first to second degree burns is with skin grafts, a process that includes taking pieces of skin from uninjured parts of the patient’s body or grafting artificial skin and grafting them over the burned area. This treatment was somewhat effective, however resulted in a recovery period of several weeks to several months. A new treatment has been developed that drastically decreases the amount of time required for a burn to heal.

A “gun” that has been developed to spray a layer of the patient’s own skin stem cells onto the wounded area has proved to be very successful. This type of treatment has been used since 2002 in Australia, Dr. Fiona Wood uses an aerosol system to spray on cultured skin cells.

The process necessary to initiate this treatment is very minimal, a biopsy is taken from the patient’s undamaged skin, healthy stem cells are isolated and an aqueous solution containing the cells is inserted into the gun and then sprayed on. The “gun” uses an electronically controlled pneumatic device that functions similar to a paint ball gun. After the cells are applied, a specially developed dressing is applied along with two sets of tubes, one functioning as an artery, supplying electrolytes, antibiotics, amino acids and glucose to the wounded area, and one set acting as a vein.

Currently, the treatment is only effective on second-degree burns, healing these within days rather than weeks or months required with previous treatments.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
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.

Filed Under: News, Stem Cell Research Tagged With: , , ,
February 3, 2011 by

New Stem Cells Found in Ovary

Parte et al. Stem Cells Dev.

Very small embryonic like cells (VSEL) are a type of stem cell that appears to be found in bone marrow and other tissues of the body, presumably as a remnant of embryonic or embryonic-like cells left over from development. In a recent paper it was demonstrated that these cells may be found in the ovary surface epithelium in adult rabbit, sheep, monkey and menopausal human.

Indian scientists found two distinct populations of putative stem cells of variable size were detected in the ovary surface epithelium: one being smaller in size around the range of 1-3 micrometers and the other being of a size approximate to the surrounding erythrocytes.

The smaller cells resembled VSELs and were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4. The larger cells were 4-7micrometers and possessed cytoplasmic localization of Oct-4 and minimal expression of SSEA-4. The scientists believed that the larger cells were possibly the progenitor germ cells.

The VSEL cells were capable of spontaneously differentiating into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype and embryonic stem (ES) cell-like colonies. They expressed Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 as detected by RT-PCR.

Germ cell markers like c-Kit, DAZL, GDF-9, VASA and ZP4 were immuno-localized in oocyte-like structures formed from the VSEL.

These studies are interesting because prior to this there were reports of bone marrow derived cells being implicated in production of oocytes. Specifically, Jonathan Tilley from Harvard reported that bone marrow transplantation can give rise to new oocytes that are donor derived http://www.ncbi.nlm.nih.gov/pubmed/17664466.

If these studies are reproducible it may be that adult stem cells could be useful in the treatment of infertility. Conversely it may be possible to repair oocytes of women who have undergone chemo/radiation therapy. Interestingly, Tilly’s group also published that ovarian tissue contains VSEL-like cells http://www.ncbi.nlm.nih.gov/pubmed/20188358

Filed Under: News, Stem Cell Research Tagged With: , , , , ,
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.

Filed Under: Adult Stem Cells, Liver, News, Stem Cell Research Tagged With: , , , ,
February 1, 2011 by

Scientists look to stem cells to mend broken hearts

Cardiac medicine has traditionally been associated with innovative procedures that sometimes where considered heretical to the present day dogma. For example, the first heart transplant, the use of the balloon catheter, the introduction of thrombolytics, all met substantial resistance from the “establishment” in their time. It appears that the next revolution in cardiac medicine is the use of stem cells. Aside from the obvious ethical and moral dilemmas surrounding embryonic tissues, the major controversy has been the belief that heart tissue does not repair itself after it has been lost. However, slowly but surely it appears that support behind the use of stem cells for heart conditions is gaining momentum.

One sign of this is the recent announcement that Britain’s leading heart charity, the British Heart Foundation (BHF), launched a 50 million pound ($80 million) research project into the potential of stem cells to regenerate heart tissue and “mend broken hearts”.

“Scientifically, mending human hearts is an achievable goal and we really could make recovering from a heart attack as simple as getting over a broken leg,” said Professor Peter Weissberg, medical director at the BHF.

One example of research in this area being performed in England is the work of Professor Paul Riley of the Institute of Child Health at University College London (UCL) who has identified a natural protein, called thymosin beta 4, that plays a role in developing heart tissue. He said his researchers had already had some success in using this protein to “wake up” cells known as epicardial cells in mice with damaged hearts. “We hope to find similar molecules or drug-like compounds that might be able to stimulate these cells further,” he told reporters at the briefing.

Currently the most advanced type of stem cell therapy for the heart involves administration of the patient’s own bone marrow cells into the area of heart damage after a heart attack. This work, which was performed in England and internationally, seems to suggest that cardiac muscle may be preserved when cells from the bone marrow produce various growth factors that stimulate stem cells that are already existing in the heart.

Other methods of administering stem cells into the heart include direct injection into the heart muscle during bypass surgery. This is performed experimentally in patients with severe angina on the hope that the injected stem cells will provide support for formation of new blood vessels, called collaterals, which are anticipated to increase the blood flow to the heart and thereby reduce angina.

Currently embryonic or fetal derived stem cells have not been used for treatment of heart conditions in humans. Therefore, at least for now, ethical issues do not seem to be a major obstacle to advancement of stem cell medicine for hearts.

Filed Under: Adult Stem Cells, Bone Marrow, Heart Disease, News, Stem Cell Research Tagged With: , , , , ,
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.

Filed Under: Adult Stem Cells, Bone Marrow, News, Stem Cell Research Tagged With: , , , ,
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.

Filed Under: Crohn's Disease, News, Stem Cell Research Tagged With: , , , , ,
January 31, 2011 by

New Cell That Keeps Stem Cells in the Bone Marrow

Chow et al. J Exp Med.

When a bone marrow transplant is performed, the bone marrow cells of the donor are injected intravenously into the recipient and somehow find their way back into the bone marrow of the recipient. The mechanism known to be responsible for this has always been cited as being SDF-1 (also called CXCL12) produced by bone marrow “stromal” cells. This mechanism is of fundamental importance to stem cell therapists for two reasons:

Firstly, stem cells are known to be recruited by injured tissue, which produces SDF-1. This has been explained as one of the mechanisms by which both cardiac and brain infarcts cause recruitment of endogenous and exogenous stem cells to the area of injury.

Secondly, by temporarily interrupting the production of SDF-1 or recognition of SDF-1 by CXCR-4, drugs such as Mozibil have been developed which are used in the mobilization of stem cells for patients who mobilize poorly in response to G-CSF.

In a paper that we view as groundbreaking, scientists found that one of the key cells in the bone marrow that produces SDF-1 is the CD169 positive macrophage. The scientists examined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced production of SDF-1 by the bone marrow.

They also found that depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce stem cell mobilization. This depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor.

Thus it appears that specific macrophage subsets play specific roles in the bone marrow stem cell system. It may be possible to use these macrophages as therapeutic agents to cause recruitment of stem cells into injured organs.

Filed Under: Adult Stem Cells, Bone Marrow, News Tagged With: , , ,
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