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

Giulia Gaggi; Andrea Di Credico; Simone Guarnieri; Maria Addolorata Mariggiò; Patrizia Ballerini; Angela Di Baldassarre; Barbara Ghinassi

doi:10.1016/j.isci.2022.105197

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

iScience. 2022 Sep 23;25(10):105197. doi: 10.1016/j.isci.2022.105197. eCollection 2022 Oct 21.

Authors

Giulia Gaggi^{1

2}, Andrea Di Credico^{1

2}, Simone Guarnieri^{2

3}, Maria Addolorata Mariggiò^{2

3}, Patrizia Ballerini⁴, Angela Di Baldassarre^{1

2}, Barbara Ghinassi^{1

2}

Affiliations

¹ Department of Medicine and Sciences of Aging, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy.
² Reprogramming and Cell Differentiation Lab, Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy.
³ Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy.
⁴ Department of Innovative Technologies in Medicine and Dentistry, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy.

Abstract

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.

Keywords: Cellular neuroscience; Developmental neuroscience; Molecular neuroscience.