hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures

Cells

Philipp Koch¹  Nathalie Couturier²  Roman Bruch²  Mathias Hafner²  Sarah Janice Hörner²  Rüdiger Rudolf² 

[1] Central Institute of Mental Health, Medical Faculty Mannheim of Heidelberg University, 68159 Mannheim, Germany;Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany;

关键词: AChR;    acetylcholine receptors;    hiPSC;    in vitro;    neural crest;    neuromuscular junction;   

DOI  :  10.3390/cells10123292

来源: DOAJ

【 摘 要 】

Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Schwann cells in these models has been hampered, due to technical limitations. Here we present robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Upon differentiation with tuned BMP signaling, Schwann cells expressed marker proteins, S100b, Gap43, vimentin, and myelin protein zero. Furthermore, they displayed typical spindle-shaped morphologies with long processes, which often aligned with motoneuron axons. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Altogether, these data argue for the availability of a consistent differentiation protocol for Schwann cells and their amenability for functional integration into neuromuscular in vitro models, fostering future studies of neuromuscular mechanisms and disease.

【 授权许可】

Unknown