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Archive - Aug 21, 2015

MSC Exosomes Activate Healing Mechanisms in Fibroblasts from Two-Year-Old Unhealed Ulcer of Patient with Uncontrolled Diabetes

Exosomes derived from mesenchymal stem cells (MSCs) were shown to be effective in stimulating wound-healing mechanisms in vitro for fibroblasts isolated from the edge of a non-healing ulcer in a 59-year-old patient with uncontrolled diabetes. The ulcer had remained unhealed for over two years, despite routine wound care, together with advanced wound care treatments. The MSC exosome work was carried out at the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine, under the leadership of Joshua M. Hare, M.D., Director of the ISCI at the University of Miami Miller School of Medicine. Dr. Hare’s team found that introducing MSC exosomes could enhance the growth and migration of normal and chronic wound fibroblasts, and induce the development of new blood vessels in vitro. Also important in wound healing is that MSC exosomes appear to induce changes by activation of growth factor signaling cascades. In particular, MSC exosomes were found to activate several signaling pathways important in wound healing (Akt, ERK, and STAT3) and to induce the expression of a number of growth factors [hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF1), nerve growth factor (NGF), and stromal-derived growth factor-1 (SDF1)]. These findings represent a promising opportunity to gain insight into how MSCs may mediate wound healing. “This study improves our understanding of MSCs and their many functions,” says Dr. Hare. “In the future, exosomes derived from MSCs could be used for wound healing as a safe and effective “off the shelf” product.” “These findings are very exciting and suggest a possible addition to the armamentarium of regenerative medicine.” This work was published online on June 29, 2015 in Stem Cells and Development.

“Possible Cure” for Genetic Obesity; New Obesity-Related Metabolic Pathway Connected with Long-Implicated FTO Gene Region; Single Base Change Can Switch Between Lean and Obese Signatures in Human Pre-Adipocytes

Obesity is one of the biggest public health challenges of the 21st century. Affecting more than 500 million people worldwide, obesity costs at least $200 billion each year in the United States alone, and contributes to potentially fatal disorders such as cardiovascular disease, type 2 diabetes, and cancer. But there may now be a new approach to prevent and even cure obesity, thanks to a study led by researchers at MIT and Harvard Medical School and published online on August 19, 2015 in an open-access article in the New England Journal of Medicine. The article is titled “FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.” “By analyzing the cellular circuitry underlying the strongest genetic association with obesity, the researchers have unveiled a new pathway that controls human metabolism by prompting our adipocytes, or fat cells, to store fat or burn it away. "Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual's metabolism," says senior author Dr. Manolis Kellis, a professor of computer science and a member of MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the Broad Institute. The strongest association with obesity resides in a gene region known as "FTO," which has been the focus of intense scrutiny since its discovery in 2007. However, previous studies have failed to find a mechanism to explain how genetic differences in the region lead to obesity. "Many studies attempted to link the FTO region with brain circuits that control appetite or propensity to exercise," says first author Dr. Melina Claussnitzer, a visiting professor at CSAIL and Instructor in Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School.