Effects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice

Nature Communications, 2022 · DOI: 10.1038/s41467-022-33134-x · Published: September 2, 2022

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how the biological sex of transplanted neural progenitor cells (NPCs) affects outcomes in spinal cord injury (SCI) treatment in mice. NPCs from male, female, or mixed-sex donors were transplanted into SCI sites in male and female mice to assess the influence of sex mismatch on graft outcomes. The research found that while the sex of donor cells did not affect graft density or axon outgrowth, male grafts in female hosts led to increased blood vessel formation (hypervascularization) and immune cell infiltration, particularly T-cells. These findings suggest that the biological sex of donor cells can trigger a sex-specific immune response in female mice, highlighting the importance of considering sex as a variable in future cell transplantation clinical trials for human SCI.

Study Duration

4 weeks

Participants

69 8–10 week-old C57BL/6 mice and 9 8–10 week-old adult female GFP mice

Evidence Level

Not specified

Key Findings

1
The biological sex of donor cells does not significantly influence graft neuron density, glial differentiation, formation of the reactive glial cell border, or graft axon outgrowth.
2
Male grafts in female hosts exhibit extensive hypervascularization, characterized by increased vascular diameter and perivascular cell density within the graft.
3
Female mice receiving male grafts show greater T-cell infiltration within the graft tissue compared to other graft types, indicating a sex-specific immune response.

Research Summary

This study examined the impact of biological sex mismatch on neural progenitor cell (NPC) transplantation outcomes in a mouse model of spinal cord injury (SCI). The research found that male NPC grafts in female hosts triggered a significant immune response, characterized by hypervascularization and increased T-cell infiltration, suggesting a sex-specific rejection mechanism. The findings emphasize the importance of considering the biological sex of donor cells in preclinical and clinical studies of cell transplantation for SCI to optimize treatment efficacy and minimize adverse immune reactions.

Practical Implications

Clinical Trial Design

Biological sex should be considered as a factor in the design of future clinical trials for cell transplantation in human SCI to minimize potential immune rejection and improve outcomes.

Preclinical Studies

Reporting the sex of donor cells in preclinical NPC transplantation studies is crucial to address variability and improve the reproducibility of research findings.

Immunological Considerations

Further research is needed to elucidate the mechanisms of sex-dependent graft rejection in SCI and NPC transplantation, including the role of H-Y antigens and hormones.

Study Limitations

1
The exact identities of the cells contained within the cell isolate upon transplantation were not characterized.
2
Behavioral outcomes were not examined in this study, limiting the assessment of functional recovery.
3
The molecular mechanisms mediating female rejection of male donor tissue were not examined.

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