Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3

Biomedicines, 2021 · DOI: https://doi.org/10.3390/biomedicines9121754 · Published: November 24, 2021

Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease (MJD), is a dominant ataxia mainly characterized by motor deficits. The study investigates mesenchymal stem cells (MSCs) as a potential therapeutic tool for CNS disorders, focusing on their neuroprotective and immunomodulatory actions. The study aimed to evaluate the effects of human MSC transplantation and human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Results indicated that a single CM administration was more beneficial than MSC transplantation, particularly in the cerebellum and basal ganglia. However, the effects observed were mild and transient.

Study Duration

25 weeks

Participants

156 male CMVMJD135 mice and wild-type littermates

Evidence Level

Preclinical trial in a mouse model

Key Findings

1
A single CM administration to the cerebellum had a mild effect on the balance and motor deficits of SCA3/MJD mice.
2
CM administration to the striatum/ substantia nigra improved the motor coordination of SCA3/MJD mice.
3
Administration of hMSCs to the spinal cord had a transient effect on the performance of treated animals when traversing the low-difficulty beams in the beam walk test.

Research Summary

This study evaluated the therapeutic potential of human mesenchymal stem cells (hMSCs) and their secretome (CM) in treating Spinocerebellar Ataxia type 3 (SCA3/MJD) using a mouse model. The results showed that CM administration, particularly to the cerebellum and basal ganglia, was more beneficial than hMSC transplantation in improving motor deficits, but the effects were mild and transient. The study suggests that while both hMSCs and CM show promise, repeated or continuous administration might be necessary to achieve sustained therapeutic effects for SCA3/MJD.

Practical Implications

Therapeutic Potential

hMSC secretome (CM) shows therapeutic potential, warranting further research as it is less invasive than cell transplantation.

Targeted Delivery

The study suggests that CM administration to specific brain regions, such as the cerebellum and basal ganglia, may be more effective in treating motor deficits in SCA3/MJD.

Treatment Regimen

Continuous or repeated administration of CM or hMSCs may be necessary to achieve sustained therapeutic benefits.

Study Limitations

1
The effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested.
2
A single administration regimen was chosen, as this is more likely to be feasible in the clinical context.
3
Unintendedly, animals treated with CM in the spinal cord had higher CAG repeat numbers when compared to the hMSC-transplanted group

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