Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy?

The ease of isolation from adult tissues, large ex vivo expansion capacity, and apparent therapeutic efficacy in a wide range of disease indications have made mesenchymal stem cells (MSCs) the stem cell of choice for regenerative medicine. Clinical and animal studies have demonstrated that secreted trophic factors, and not stem cell differentiation, likely mediated much of the therapeutic efficacy of MSCs. This paradigm shift in the therapeutic mechanism of MSCs has started to transform MSC therapy from a cell- to biologic-based therapy. Our group has identified the exosome, a secreted membrane vesicle, as an active therapeutic factor in MSC secretion. An exosome is thought to mediate cell to cell communication. It carries a large and varied protein cargo that could regulate a wide array of biochemical and cellular processes. These include enhancing glycolysis which increases not only cellular ATP production but also glycolytic intermediates for anabolic activities, inducing adenosine-mediated activation of survival kinases (e.g., ERK and AKT via CD73) and reducing complement activation through CD59. As these ­processes are fundamental, non-tissue specific processes in ameliorating tissue injury and promoting tissue repair, MSC exosomes could potentially underpin the therapeutic efficacy of MSC in diverse disease indications. This could transform present MSC-based therapies into MSC exosome-based therapies.