RRC ID 51724
Author Suto N, Mieda T, Iizuka A, Nakamura K, Hirai H.
Title Morphological and Functional Attenuation of Degeneration of Peripheral Neurons by Mesenchymal Stem Cell-Conditioned Medium in Spinocerebellar Ataxia Type 1-Knock-in Mice.
Journal CNS Neurosci Ther
Abstract AIMS:Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin-1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration. We previously showed that intrathecal injection of mesenchymal stem cells (MSCs) during the nonsymptomatic stage mitigates the degeneration of the peripheral nervous system (PNS) neurons in SCA1-knock-in (SCA1-KI) mice. We tested in this study whether the therapeutic effects of MSCs in SCA1-KI mice could be reproduced with MSC-releasing factor(s).
METHODS:To test the effects of MSC-releasing factor(s), we used MSC-conditioned medium (MSC-CM). MSC-CM was intrathecally and/or intravenously injected into young SCA1-KI mice, and the therapeutic effects were assessed in the PNS at later ages using immunostaining, electrophysiology, and behavioral tests.
RESULTS:MSC-CM attenuated the degeneration of axons and myelin of spinal motor neurons. Consequently, the injected SCA1-KI mice exhibited smaller reductions in nerve conduction velocity in spinal motor neurons and reduced motor incoordination than the untreated mice.
CONCLUSIONS:These results suggest that factors released from MSC mitigate the morphological and functional abnormalities in the PNS that are observed in SCA1-KI mice in a paracrine manner.
Volume 22(8)
Pages 670-6
Published 2016-8-1
DOI 10.1111/cns.12560
PMID 27140210
PMC PMC6492824
MeSH Age Factors Animals Ataxin-1 / genetics* Ataxin-1 / metabolism Axons / drug effects Axons / pathology Cells, Cultured Culture Media, Conditioned / pharmacology* Disease Models, Animal Evoked Potentials, Motor / physiology Humans Mesenchymal Stem Cells / chemistry* Mesenchymal Stem Cells / physiology Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity / drug effects Motor Neurons / metabolism Myelin Basic Protein / metabolism Nerve Degeneration / drug therapy* Nerve Degeneration / etiology* Reaction Time / drug effects Spinocerebellar Ataxias / complications* Spinocerebellar Ataxias / genetics Spinocerebellar Ataxias / metabolism Tubulin / metabolism
IF 3.495
Times Cited 8
Human and Animal Cells KUM10(RCB2295)