Fully Characterized Mature Human iPS- and NMP-Derived Motor Neurons Thrive Without Neuroprotection in the Spinal Contusion Cavity

Frontiers in Cellular Neuroscience

Cinzia Stigliano¹  Philip J. Horner¹  Jose Cibelli³  Zachary T. Olmsted⁴  Janet L. Paluh⁴  Brandon Marzullo⁵ 

[1] Center for Neuroregeneration, Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX, United States;Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, United States;Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States;Nanobioscience Constellation, Colleges of Nanoscale Science and Engineering, State University of New York Polytechnic Institute, Albany, NY, United States;SUNY Buffalo Genomics and Bioinformatics Core, New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, United States;

关键词: spinal cord injury;    spinal motor neuron;    neuromesodermal progenitor;    oligodendrocyte progenitor cell;    neuron transplantation;    neuron survival;   

DOI  :  10.3389/fncel.2021.725195

来源: DOAJ

【 摘 要 】

Neural cell interventions in spinal cord injury (SCI) have focused predominantly on transplanted multipotent neural stem/progenitor cells (NSPCs) for animal research and clinical use due to limited information on survival of spinal neurons. However, transplanted NSPC fate is unpredictable and largely governed by injury-derived matrix and cytokine factors that are often gliogenic and inflammatory. Here, using a rat cervical hemicontusion model, we evaluate the survival and integration of hiPSC-derived spinal motor neurons (SMNs) and oligodendrocyte progenitor cells (OPCs). SMNs and OPCs were differentiated in vitro through a neuromesodermal progenitor stage to mimic the natural origin of the spinal cord. We demonstrate robust survival and engraftment without additional injury site modifiers or neuroprotective biomaterials. Ex vivo differentiated neurons achieve cervical spinal cord matched transcriptomic and proteomic profiles, meeting functional electrophysiology parameters prior to transplantation. These data establish an approach for ex vivo developmentally accurate neuronal fate specification and subsequent transplantation for a more streamlined and predictable outcome in neural cell-based therapies of SCI.

【 授权许可】

Unknown