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CNS Neurosci Ther. 2016 Aug;22(8):670-6. doi: 10.1111/cns.12560. Epub 2016 May 3.

Morphological and Functional Attenuation of Degeneration of Peripheral Neurons by Mesenchymal Stem Cell-Conditioned Medium in Spinocerebellar Ataxia Type 1-Knock-in Mice.

Author information

1
Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
2
Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

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.

KEYWORDS:

Axon; Conditioned medium; Mesenchymal stem cell; Myelin; SCA1; Spinal motor neuron

PMID:
27140210
DOI:
10.1111/cns.12560
[Indexed for MEDLINE]

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