Prof. Dr. med. Bodo-Eckehard Strauer did his first clinical treatment using adult stem cell transplant for a heart patient on March 30, 2001, over ten years ago. Since that time, he and his team have treated hundreds of patients, have published a text on such heart treatments, and many other groups around the world have used adult stem cells for treatment of heart disease.

Now Prof. Dr. med. Strauer and his colleague, Prof. Dr. med. Gustav Steinhoff, have published a review of the field of adult stem cell therapy for heart:

10 Years of Intracoronary and Intramyocardial Bone Marrow Stem Cell Therapy of the Heart: From the Methodological Origin to Clinical Practice

The paper is published as a “State-of-the-Art Paper” in Journal of the American College of Cardiology. It is far more than a historical overview. The paper discusses the rationale for use of adult stem cells to repair cardiac tissue, examines various routes of administration to the heart as well as possible mechanisms of action, documents the effectiveness in studies treating acute as well as chronic heart damage including chronic dilated cardiomyopathy, and provides perspectives for future studies to improve heart treatments. Regarding previous studies of adult stem cells for heart therapy, the authors note:

Thus, the therapeutic advantage clearly prevails, and clinical use has already been realized.

and point to the future

“Interest should be focused on adult stem cell projects that have already proven significant clinical efficacy, but without having any ethical concerns.”

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Hard to lose this kitty in the dark, since it fluoresces a green color. Mayo clinic researchers have created a transgenic cat, genetically engineered to glow green. They used a technique called gamete-targeted lentiviral transgenesis, inserting genes into cat oocytes before fertilization with normal sperm. This was the first time the technique had succeeded with a carnivore. Besides inserting the GFP (green fluorescent protein) gene, which was actually used for tracking purposes, they also inserted a gene from rhesus monkeys–TRIMCyp–that is a “restriction factor”, known to block Feline Immunodeficiency Virus (FIV), the feline equivalent of the human AIDS virus (HIV). When some of the kittens glowed green, it was evidence that the FIV-blocking gene had been successfully transferred. The successful gene transfer was also verified by the ability of the transgenic cats to pass on their glowing personality to their offspring (F1 generation), showing that the transferred genes were present in the germline.

According to researchers, cats are valuable models for the study of numerous human conditions. This line of cats will help studies related to FIV and HIV infection. Initial tests already show that the blood cells of the transgenic cats are resistant to growth of the FIV virus.

Previous attempts to generate genetically-engineered cats tried to use cloning techniques (somatic cell nuclear transfer; SCNT), but the authors note in relation to SCNT cloning:

“However, the efficiency of animal cloning is extremely low, and SCNT results in faulty epigenetic reprogramming in most embryos. Cloned mammals with apparently normal gross anatomy can have many abnormalities resulting from failure to erase and reprogram epigenetic memory completely.”

In short, SCNT cloning has been an abysmal failure. But the technique used by the Mayo Clinic scientists is supposedly much better. According to senior author Dr. Eric Poeschla:

“The 23% success rate is much higher than the typical 3% seen with somatic cell nuclear transfer. Almost all of our pregnancies were transgenic, and that efficiency is important so you don’t have to extensively screen these large animals. The really great thing is that the animals were healthy and fertile and their kittens were healthy.”

The article is published in the journal Nature Methods.

Note that is not the first green fluorescent cat; Mr. Green Genes made his debut in October 2008. And will the green-fluorescent cat be chased by the red-fluorescent dog?

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Scientists have shown for the first time that cultured red blood cells can be grown in the lab from adult stem cells and injected successfully into a human. While embryonic stem cells produce only unsuitable, immature cells, with rejection and uncontrolled tumor growth remaining a concern as well, by contrast adult stem cells can efficiently produce healthy, safe cells for transfusion.

French scientists took hematopoietic stem cells (HSC’s; the adult stem cells that form all blood cells) from a human donor and from those cells, generated billions of “cultured red blood cells” (cRBC’s) in the laboratory. They first tested the function of the cells by injection into mice, showing that the lab-generated cells were able to mature fully.

Then they took adult stem cells from a human volunteer donor, made more cells in the lab, and injected ten billion cells back into the human donor. The cells survived and functioned comparable to normal red blood cells.

Dr. Luc Douay, senior study author, noted:

“Although previous research has shown that HSCs can be developed into fully matured red blood cells, this is the first study that has proven that they are capable of survival in the human body, a major breakthrough for the transplant community. The results from our study establish the feasibility of the concept of transfusing cRBCs and show promise that an unlimited blood reserve is within reach. Although the full-scale production of these cells will require additional technological advances in cell engineering, we believe cRBCs could prove to be a valid alternative to classic transfusion products that will not only provide an adequate supply of blood, but reduce the risk of life-threatening complications and infections that can accompany traditional transfusion.”

The study was published online in the journal Blood.

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An international research team has become the first to isolate and grow adult stem cells from human colon. Scientists have long known that throughout life, adult stem cells of the colon regenerate the inner layer of our large intestine on a weekly basis. But it has previously been impossible to grow these adult stem cells successfully in the laboratory. Working together, scientists from Spain, Japan, and the Netherlands have established the conditions to maintain living human colon stem cells (CoSCs) outside of the human body long-term: According to first author Peter Jung:

“This is the first time that it has been possible to grow single CoSCs in lab-plates and to derive human intestinal stem cell lines in defined conditions in a lab setting. Now we can maintain stem cells in a plate up to 5 months or we can induce these cells to differentiate artificially, as they do inside our bodies. This achievement opens up an exciting new area of research with the potential to bring about a huge breakthrough in regenerative medicine,”

According to Jung, the main elements for making regenerative medicine a reality, namely adult stem cells, are just starting to be understood. The ability to grow and study colon stem cells in the lab may lead to insights regarding numerous intestinal diseases, including Crohn’s disease. The report is publshed in the journal Nature Medicine.

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Duke University scientists have unraveled the controls in the brain that produce new neurons from adult stem cells throughout life. Using a mouse model, they found that the neural stem cells’ neighbors, called “ependymal cells”, are important in providing an environment that keeps neural stem cells young and able to continually make new neurons.

The scientists discovered that a sequence of events made the neighborhood, or stem cell “niche”, conducive to neuron production. The sequence started with the neighbors, the ependymal cells. A protein called Foxj1, which turns on specific genes in cells, turned on a structural protein called Ankyrin in the ependymal cells, and subsequently these support cells formed an interlaced pinwheel-like architecture surrounding the adult neural stem cells. The structural support including as-yet-unidentified signals instructs neural stem cells to continue neuron production.

Dr. Chay Kuo, senior author on the research study published in the journal Neuron, said:

“”There is this fountain of youth inside the adult brain that actively makes new neurons. We believe these findings will have important implications for human therapy.”

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The da Vinci surgical robot is used to perform precise surgical procedures in a small space, typically making various surgeries minimally invasive and leading to shorter recovery times for patients.

As a demonstration of the robot’s precision, Dr. James Porter of the Swedish Medical Center in Seattle used the robot to make a tiny paper airplane.

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Susan Cossabone is growing new leg bone thanks to adult stem cells. She was in a terrible head-on collision, and thought her injured leg would have to be amputated.

“I thought I would lose the leg. If you could have seen it when they cut off my favorite jeans — you could just see bones sticking and flesh. You couldn’t see much of a leg.”

But world-renowned foot and ankle specialist Dr. Mark Myerson of Baltimore’s Mercy Medical Center used adult stem cells to help regrow the bone in her leg, and now she is beginning to walk again.

Sites for the approved clinical trial include Baltimore, MD, Grand Rapids, MI, and Edina, MN (see the link for details.)

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A new report suggests that stimulating adult stem cells might treat baldness, growing hair on heads that are bare. Previous work has shown that adult stem cells are still present in the hair follicles of the skin of bald men, in the follicle roots, but the stem cells have lost the ability to begin hair regeneration. Hair follicle stem cells need signals from within the skin to grow hair, but the source of those signals has been unclear until now.

Yale researchers used a mouse model to show that hair regeneration requires a type of stem cell, an adipose precursor, that forms new skin fat cells. These stem cells also produce a molecule called PDGF (platelet-derived growth factor) that stimulates other skin stem cells for hair growth. Senior author Valerie Horsley said:

“If we can get these fat cells in the skin to talk to the dormant stem cells at the base of hair follicles, we might be able to get hair to grow again.”

The results are published in the journal Cell.

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Canadian scientists have published data that indicate exercise stimulates adult stem cells to form bone instead of fat. The scientists used a mouse model to study exercise effects on adult bone marrow stem cell and blood production. Using treadmill-conditioned mice, they found that aerobic exercise triggers adult stem cells to become bone more often than fat. The bone environment provides better conditions, called a “niche”, for adult blood stem cell development. When the mice were sedentary, the stem cells tended to form fat, which impairs blood production in bone marrow cavities.

Dr. Gianni Parise, senior author on the study, said:

“The interesting thing was that a modest exercise program was able to significantly increase blood cells in the marrow and in circulation. What we’re suggesting is that exercise is a potent stimulus — enough of a stimulus to actually trigger a switch in these [adult] stem cells. Exercise has the ability to impact stem cell biology. It has the ability to influence how they differentiate.”

The results were published online before print in The FASEB Journal.

Previous studies have shown that exercise can increase the number of muscle adult stem cells, the number of new brain neurons from adult stem cells, and the number of neural adult stem cells.

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Scientists have published evidence that eating chocolate can decrease risk of heart disease. The paper analyzed and combined the results of seven separate studies, involving over 114,000 participants. Results indicated that high levels of chocolate consumption might be associated with a one third reduction in the risk of developing heart disease. The scientists also note that more studies are needed to determine whether it is actually the chocolate consumption or some other factor that they didn’t analyze, that was responsible for the increased heart health. The studies looked at the consumption of dark chocolate as well as milk chocolate, chocolate drinks and other chocolate confectionaries.

Dr. Oscar Franco, senior author on the study, said:

“Chocolate may be beneficial, but it should be eaten in a moderate way, not in large quantities and not in binges. If it is consumed in large quantities, any beneficial effect is going to disappear.”

The analysis was published in the British Medical Journal, as an open-access study; that means you can read the paper for free (but the chocolate costs extra.)

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Adult stem cells are safe as well as feasible for treatment of stroke in patients, according to the published results of a ground-breaking Phase I trial from the University of Texas Health Science Center at Houston. Looking at ten patients in this first study, the researchers found no study-related severe adverse events, and while the study was not designed to determine effectiveness, the team found that most of the patients did better compared with matched untreated patients.

Dr. Sean Savitz, first author, said:

“In order to bring stem cells forward as a potential new treatment for stroke patients, we have to establish safety first and this study provides the first evidence in addressing that goal. Now we are conducting two other stroke cell therapy studies examining safety and efficacy, one of which can be administered up to 19 days after someone has suffered a stroke.”

Results of the study were published in the journal Annals of Neurology.

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Adding a specific gene to adult stem cells from bone marrow might be used to increase cancer resistance of transplant patients. A University of Kentucky team led by Dr. Vivek Rangnekar studied bone marrow adult stem cells from mice, that were genetically engineered to express a cancer-killing portion of a protein known as Par-4. Par-4 is a “tumor suppressor” protein that selectively induces cellular suicide (known as “apoptosis”) in cancer cells, but not normal cells. The scientists found that the mice were resistant to the growth of various types of tumors. Further, the cancer resistance could be transferred to other, normal mice by a bone marrow adult stem cell transplant. The scientists said that optimizing the adult stem cell transplant of genetically modified cells might be used to treat various tumors, including metastatic tumors.

The study was published in the journal Cancer Biology & Therapy.

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Stress can stimulate production of new adult neural stem cells. An area of the brain known as the hippocampus responds to environmental conditions, including stress such as being held in isolation, and produces new neural stem cells that are stockpiled for later use. As conditions become more favorable, such as being moved to an enriched environment with various stimuli, the neural stem cells can be used to produce new brain neurons. The new study, published in the journal Neuron, shows that adult stem cell production in the brain is responsive to experience and the environment, indicating that this may act as a form of cellular plasticity for adapting to environmental changes.

A new paper published in the journal Nature further suggests that if those stored neural adult stem cells are not used to produce new neurons, you could be more susceptible to depression. NIH researchers found that new neurons formed by adult stem cells in the brain could protect against depression and stress in a mouse model. However, mice that could not form new neurons had elevated levels of stress hormones and showed more depressive behaviors. The authors note that their results provide evidence to support a direct role for adult neuron formation in depressive illness.

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Think positive, Eeyore! Optimism may lower the risk of stroke. Stroke is the third leading cause of death in the United States. The study published in the journal Stroke, looked at 6,044 adults over the age of 50, and correlated their self-reported optimism with a decrease in acute stroke risk over a two-year period. For every point increase on a standard cognitive test for optimism (a 16-point scale), stroke risk decreased by 9 percent.

The researchers note that the protective effect of optimism may be due to behavioral choices, such as taking vitamins, eating a healthy diet and exercising, but some evidence suggests positive thinking might have a strictly biological impact as well. Previous research has shown that an optimistic attitude is associated with better heart health outcomes and enhanced immune-system functioning, among other positive effects.

After a stroke, keep a positive attitude as well. Promising early results have been seen using adult stem cells to treat stroke.

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For those keeping track, late yesterday NIH Director Francis Collins approved four more human embryonic stem cell (hESC) lines for the embryonic stem cell registry. The four newest approvals are sold by the company BioTime, Inc., which had two other hESC lines approved June 2, 2011. Details of the embryo destruction and hESC derivation (including from siblings) were published by ESI and Sydney IVF workers in 2007, around the time that ESI abandoned its schemes for therapies based on hESC. BioTime subsequenctly acquired ESI in 2010.

The total number of approved hESC lines is now 132, after a push of approvals earlier this year at NIH. While NIH continues to waste more taxpayer funds on destructive embryo research, adult stem cells are the only stem cell treating patients, with more and more published evidence accumulating every week. Published scientific evidence over the last few months shows effectiveness of adult stem cells in helping patients with angina pain, aggressive multiple sclerosis, enlarged hearts, systemic sclerosis, and creating new windpipes, to name just a few examples of adult stem cell successes.

Adult stem cells remain the gold standard for actual patient treatments.

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Scientists at Harvard today have published a new report in the journal Cell Stem Cell, showing that ordinary fibroblasts can be directly converted into functioning motor neurons. Starting with easily-accessible mouse fibroblasts, a common cell type found in connective tissue and skin, they added a set of genes that induced generic neuronal specialization, as well as a set of genes specific for a specific nerve type, the spinal motor neuron. The initial combination of eleven genes directly converted the fibroblast cells into specific neuronal cells. In the end, a set of seven genes added to common fibroblast cells was sufficient for direct conversion to functional spinal motor neuron cells. The converted cells not only looked like neurons, but showed a gene expression pattern similar to normal spinal motor neurons, were electrically active like normal nerve cells, and could form connections in the lab dish with muscle cells and stimulate muscle contraction. When injected into developing chicken embryos, the converted cells took up normal residence in the spinal cord.

The group verified that the formation of the spinal motor neurons was due to direct conversion, and did not go through any stem cell intermediate stage. They also showed that human fibroblasts could be directly converted into functional spinal motor neurons using a set of eight neuronal genes. The ability to make specific neurons directly from common adult cells, in an ethical manner, could allow production of patient-specific cells for study of specific motor neuron characteristics, disease susceptibility, and potential drug therapies. There has been a spate of papers showing direct conversion of normal cells to nerve cells. This new paper makes the eighth paper in the last three months. That’s a lot of nerve!

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Like an out of control youth, embryonic stem cells can wreak havoc with tissue damage and tumor formation. Their inability to make appropriate, mature cells that can function in an adult body is also a problem. Scientists at UCLA have found that cells derived from pluripotent stem cells are developmentally very immature, and do not resemble the adult cell types that they would theoretically replace in a transplant. The immaturity was seen in cell derivatives from both embryonic stem cells and induced pluripotent stem (iPS) cells. The data indicate that pluripotent stem cells such as embryonic stem cells are inappropriate substitutes for adult stem cells in patient treatments.

One goal of the UCLA study was to address the ongoing question of just how closely iPS cells resemble embryonic stem cells. The researchers derived several different cell types from both human embryonic stem cells and human iPS cells–neuronal cells, hepatocytes (liver cells), and fibroblasts (common in skin and connective tissue.) The progeny of the human pluripotent stem cells were compared to each other by gene expression patterns, functionality and appearance. The authors noted that the two cell types “make nearly identical progeny”, with essentially no difference between them, again indicating that iPS cells can substitute for embryonic stem cells in laboratory studies.

But when the scientists compared the cells made from pluripotent stem cells to normal human tissue cells, there were significant differences in gene expression patterns. Cells made from embryonic stem cells and iPS cells had not turned off many of the genes normally expressed only in growing, pluripotent stem cells. According to senior author Dr. William Lowry, this could be very problematic, since some of those same pluripotency genes are expressed during cancer development. The cells derived from embryonic stem cells were developmentally very immature, and were most similar to cells less than six weeks after conception, in the earliest stages of human development. Lowry said:

“What we found, looking at gene expression, was that the cells we derived were similar to cells found in early fetal development and were functionally much more immature than cells taken from human tissue. This finding may lead to exciting new ways to study early human development, but it also may present a challenge for transplantation, because the cells you end up with are not something that’s indicative of a cell you’d find in an adult or even in a newborn baby.”

Other groups have previously documented similar results, that embryonic stem cells produce immature cells, and that embryonic stem cell derivatives are inappropriate for use in transplants. This new study published in the journal Cell Research shows the developmental level to be very immature. These are critical discrepancies that could be lethal during transplantation, again indicating that embryonic stem cell derivatives are inappropriate for therapies.

Meanwhile, adult stem cells continue to treat over 50,000 patients a year around the globe.

Adult stem cells remain the gold standard for actual patient treatments.

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Japanese scientists have shown that useful adult stem cells can be isolated from the human ear. The cells come from a part of the ear called the perichondrium, which is a thin layer of connective tissue that covers and protects cartilage in the human body. Previously another group had shown the regenerative potential of adult stem cells from rabbit ears, but the new study is the first to show such adult stem cells present in the human ear.

Prof. Shinji Kobayashi, lead author on the study published in the Proceedings of the National Academy of Sciences, and his colleagues discovered adult stem cells from the membrane that covers cartilage in the human ear. They developed a technique to grow the adult stem cells into cartilage efficiently, and found that the human stem cell-derived cartilage was stable for at least 10 months after it was transplanted under the skin of mice.

As the authors note in their published paper, there is great demand for effective treatments for craniofacial injuries or abnormalities, but effective treatments are currently lacking. Their discovery of this new, easily-accessible source of adult stem cells and their technique for efficient growth of cartilage would allow patients suffering from craniofacial deformities to be treated with reconstructive material grown from adult stem cells collected from their own ears. The scientists hope to start a clinical study as early as 2012.

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Greg Pollowitz over at National Review Online has a brief post about a disturbing article at Wired; Pollowitz titles his post “Josef Mengele Now Writing for Wired Magazine?” Before you condemn that as harsh, check out the article mentioned, titled “Seven Creepy Experiments That Could Teach Us So Much (If They Weren’t So Wrong)” and decide for yourself if these proposals are creepy, or even if you consider them wrong. Perhaps what is really creepy, as well as sad, is that some supposedly serious scientists don’t really consider these or other equally disturbing proposals unethical or creepy, but simply “interesting science”, even worth pursuing for the greater good, or holding great potential for scientific or medical breakthroughs and cures (the most common justification). The question really is, what makes these proposed experiments so wrong? Is it because these are experiments on human beings, that manipulate humans? Is any human life valuable, are all humans valuable? Worth pondering in terms of what we deem wrong or unethical.

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A study by University of Minnesota Medical School researchers shows that mobilizing adult stem cells from bone marrow is safe for the adult stem cell donors. Many people are familiar with “bone marrow transplants”, which are actually “adult stem cell transplants”, though it wasn’t until the 1990′s that the first human adult stem cell was successfully isolated and purified. Bone marrow adult stem cell donors provide a life‑saving donation of cells for people with various cancers, anemias, and a growing number of other conditions. Collecting the life‑saving adult stem cells directly from bone marrow is a surgical outpatient procedure. But the adult stem cells can also be collected from peripheral blood. Donors can be given a protein growth factor/drug called granulocyte colony‑stimulating factor (G‑CSF; also called filgrastim or Neupogen). This stimulates adult stem cells to move out of the bone marrow and into the blood stream, a process called mobilization. Once in the blood, large doses of adult stem cells can be collected safely and without surgery by a process called apheresis, avoiding bone marrow harvest in the operating room.

Since 2003, over 70% of “bone marrow” or “stem cell” donors have been asked to donate mobilized cells from peripheral blood (Peripheral Blood Stem Cells, PBSC.). Donor adult stem cells are used in a little less than half of the over 50,000 adult stem cell transplants done every year. Previously, there had been some concern that high doses of G-CSF given to donors might result in abnormalities in donors’ cells.

The current study, which was published in the journal Blood, shows that it is unlikely that the mobilization procedure puts healthy stem cell donors at risk for later development of cell abnormalities. Dr. Jeffrey McCullough, senior author on the study, said:

“Furthermore, our data support the conclusion that G‑CSF does not induce chromosomal instability through the PBSC mobilization process and remains a safe therapy for healthy stem cell donors.”

Adult stem cells remain the gold standard for actual patient treatments.

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