High-density ZnO Nanowires as a Reversible Myogenic-Differentiation-Switch

Mesoangioblasts are outstanding candidates for stem cell therapy and are already being explored in clinical trials. However, a crucial challenge in regenerative medicine is the limited availability of undifferentiated myogenic progenitor cells, since growth is typically accompanied by differentiation. Here reversible myogenic-differentiation-switching during proliferation is achieved by functionalizing the glass substrate with high-density ZnO nanowires. Specifically, mesoangioblasts grown on ZnO nanowires present a spherical viable undifferentiated cell state without lamellopodia formation during all the observation time (8 days). Consistently, the Myosin Heavy Chain, typically expressed in skeletal muscle tissue and differentiated myogenic progenitors, is completely absent. Remarkably, nanowires do not induce any damage while reversibly block differentiation, so that the differentiation capabilities are completely recovered upon cells removal from the nanowires-functionalized substrate and re-plating on standard culture glass. This is the first evidence of a reversible myogenic-differentiation switch which does not affect viability. These results can be the first step toward the in vitro growth of a large number of undifferentiated stem/progenitor cells and therefore can represent a breakthrough for cell based therapy and tissue engineering.