Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits.

Acta Neuropathologica Communications
Genevieve M SullivanRegina C Armstrong

Abstract

Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice. Male C57BL/6 mice fed 0.3% cuprizone for 12 weeks exhibited CC atrophy with chronic demyelination, astrogliosis, and microglial activation. Syngeneic iNSCs were transplanted into the CC after ending cuprizone and perfused for neuropathology 2 weeks later. Magnetic resonance imaging (MRI) sequences for magnetization transfer ratio (MTR), diffusion-weighted imaging (T2), and diffusion tensor imaging (DTI) quantified CC pathology in live mice before and after iNSC transplantation. Each MRI technique detected progressive CC pathology. Mice that received iNSCs had normalized DTI radial diffusivity, and reduced astrogliosis post-imaging. A motor skill task that engages the CC is Miss-step wheel running, which demonstrated functional deficits from cuprizone demyelination. Transplantation of ...Continue Reading

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Citations

Dec 1, 2020·Frontiers in Cellular Neuroscience·Cory M WillisStefano Pluchino
Mar 30, 2021·Frontiers in Bioengineering and Biotechnology·Kathryn M KimRobert A Marr
May 15, 2021·Cell & Bioscience·Tianyuan Shi, Martin Cheung
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Jayden A SmithStefano Pluchino

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Key Resources (RRID) Mentioned

IMSR_JAX
AB_2341193
AB_2753197
AB_10013382
AB_776174
AB_2535813
AB_2535858
AB_2313568
AB_2338707
AB_1587278

Software Mentioned

ImageJ
Excel RAND
MATLAB
ImageJ Plug -
VivoQuant
GraphPad Prism
NIH
Activity Wheel Monitor
Zen
TORTOISE

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