Human Motor Neuron Progenitor Transplantation Leads to Endogenous Neuronal Sparing in 3 Models of Motor Neuron Loss

Abstract

Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

Myelination of Motor Neurons Derived from Mouse Embryonic Stem Cells by Oligodendrocytes Derived from Mouse Embryonic Stem Cells in a Microfluidic Compartmentalized Platform

“…Transplanted motor neurons may replace the lost MNs. Studies have shown that transplanted ESCs derived MNs supported the endogenous neurons survival through secretion of beneficial growth factors in the SCI model [27], spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS) model [28]. Transplanted OPCs may differentiate into mature oligodendrocytes to myelinate both ESCs derived MNs and constitutive MNs.…”

The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

“…Moreover, the intrathecal injection of neural stem cells in SMA mice has been proved to increase animal survival ameliorating their phenotype [42,43].…”

Cellular toxicity induced by the 26‐kDa fragment and amyotrophic lateral sclerosis‐associated mutant forms of TAR DNA‐binding protein 43 in human embryonic stem cell‐derived motor neurons

“…Therefore, the primary aim of the present study was to explore the cytotoxicity of the 35-kDa and 26-kDa fragments, as well as the p.A315T and p.A382T mutants, against human embryonic stem (ES) cell-derived motor neurons. 13 RNA editing at the Q/R site of AMPA receptor subunit 2 (GluA2) mRNA is reportedly insufficient in the spinal motor neurons of sporadic ALS patients.…”