Human fetal membrane-mesenchymal stromal cells generate functional spinal motor neurons in vitro

Human fetal membrane mesenchymal stromal cells (hFM-MSCs) are a cell population easily isolable from the amniochorionic membrane of term placentas, without ethical issues or safety limitations. We previously reported that hFM-MSCs share some epigenetic characteristics with pluripotent stem cells and can overcome the mesenchymal commitment. Here, we demonstrated that hFM-MSCs can give rise to spinal motor neurons by the sequential exposure to specific factors that induced a neuralization, caudalization and ventralization of undifferentiated cells, leading to a gradual gene and protein upregulation of early and late MN markers. Also, spontaneous electrical activity (spikes and bursts) was recorded. Finally, when co-cultured with myotubes, differentiated MNs were able to create functional neuromuscular junctions that induced robust skeletal muscle cell contractions. These data demonstrated the hFM-MSCs can generate a mature and functional MN population that may represent an alternative source for regenerative medicine, disease modeling or drug screening.