Mesenchymal stem cell conditioned medium increases glial reactivity and decreases neuronal survival in spinal cord slice cultures

Biochemistry and Biophysics Reports, 2021 · DOI: https://doi.org/10.1016/j.bbrep.2021.100976 · Published: February 22, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how mesenchymal stem cell conditioned medium (MSC CM) affects spinal cord tissue in a lab setting. Spinal cord slice cultures (SCSC) were treated with MSC CM, and researchers observed changes in cell survival, astrocyte activity and neuronal processes. The results showed that MSC CM enhanced the viability of the spinal cord slices and increased the activity of astrocytes, a type of glial cell. However, it also led to a decrease in the prevalence of neuronal processes. These findings suggest that while MSC CM may have some beneficial effects on spinal cord tissue, such as promoting cell survival, it can also negatively impact neuronal growth, highlighting the complexity of using MSC-based therapies for spinal cord injuries.

Study Duration

Not specified

Participants

9 mixed gender CD1 mouse pups (postnatal day 7–11)

Evidence Level

Ex vivo study

Key Findings

1
MSC CM increased astrocytic reactivity, as evidenced by increased GFAP immunostaining and astrocytic process length in SCSC compared to control medium.
2
MSC CM significantly decreased the prevalence of βIII-tubulin immunoreactive neurites, indicating a reduction in neuronal cell processes in the treated SCSC.
3
Calcium imaging revealed a significant increase in calcium oscillations in active cells within MSC CM compared to controls, suggesting altered cellular signaling activity.

Research Summary

The study aimed to assess the effects of canine MSC CM on murine SCSC, focusing on cell survival, astrocyte reactivity, CSPG levels, and neuronal cell processes. Results indicated that MSC CM enhanced cell survival and promoted astrocytic hypertrophy within SCSC, but did not affect CSPG levels in glia. Conversely, MSC CM reduced neurite extension in cultured neurons and the number of active cells, while paradoxically increasing the frequency of Ca2+ transients in the remaining active cells.

Practical Implications

Refining Cell Therapies

The study emphasizes the need for careful comparison of different experimental conditions when assessing the potential of cell therapies for treating spinal cord injury.

Understanding MSC Mechanisms

Further research is required to fully understand the mechanisms by which MSC CM exerts its effects and why these effects differ between in vitro cell cultures and SCSC.

Model System Selection

The observed differences between MSC CM effects in vitro, ex vivo, and in vivo underscore the importance of selecting appropriate model systems to study the impact of cell transplants and secreted factors on the CNS.

Study Limitations

1
The SCSC were cultured without corresponding circulatory models, which could alter how resident cells respond to the MSC.
2
The study acknowledges a lack of identification of specific neurotrophic factors within the MSC CM responsible for the observed changes.
3
The study used murine SCSC while the MSC CM was derived from canine cells, which may introduce species-specific effects.

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