Extracellular Vesicles from Skeletal Muscle Cells Efficiently Promote Myogenesis in Induced Pluripotent Stem Cells

• Main Authors: Denisa Baci, Maila Chirivì, Valentina Pace, Fabio Maiullari, Marika Milan, Andrea Rampin, Paolo Somma, Dario Presutti, Silvia Garavelli, Antonino Bruno, Stefano Cannata, Chiara Lanzuolo, Cesare Gargioli, Roberto Rizzi, Claudia Bearzi
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Cells
• Subjects: iPSC; extracellular vesicles; pericytes; skeletal muscle
• Online Access: https://www.mdpi.com/2073-4409/9/6/1527

The recent advances, offered by cell therapy in the regenerative medicine field, offer a revolutionary potential for the development of innovative cures to restore compromised physiological functions or organs. Adult myogenic precursors, such as myoblasts or satellite cells, possess a marked regenerative capacity, but the exploitation of this potential still encounters significant challenges in clinical application, due to low rate of proliferation in vitro, as well as a reduced self-renewal capacity. In this scenario, induced pluripotent stem cells (iPSCs) can offer not only an inexhaustible source of cells for regenerative therapeutic approaches, but also a valuable alternative for in vitro modeling of patient-specific diseases. In this study we established a reliable protocol to induce the myogenic differentiation of iPSCs, generated from pericytes and fibroblasts, exploiting skeletal muscle-derived extracellular vesicles (EVs), in combination with chemically defined factors. This genetic integration-free approach generates functional skeletal myotubes maintaining the engraftment ability in vivo. Our results demonstrate evidence that EVs can act as biological “shuttles” to deliver specific bioactive molecules for a successful transgene-free differentiation offering new opportunities for disease modeling and regenerative approaches.