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.
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