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

Michael Pitonak, Miriam Aceves, Prakruthi Amar Kumar, Gabrielle Dampf, Peyton Green, Ashley Tucker, Valerie Dietz, Diego Miranda, Sunjay Letchuman, Michelle M. Jonika, David Bautista, Heath Blackmon and Jennifer N. Dulin ()
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Michael Pitonak: Texas A&M University
Miriam Aceves: Texas A&M University
Prakruthi Amar Kumar: Texas A&M University
Gabrielle Dampf: Texas A&M University
Peyton Green: Ganado High School
Ashley Tucker: Texas A&M University
Valerie Dietz: Texas A&M University
Diego Miranda: Texas A&M University
Sunjay Letchuman: Texas A&M University
Michelle M. Jonika: Texas A&M University
David Bautista: Texas A&M University
Heath Blackmon: Texas A&M University
Jennifer N. Dulin: Texas A&M University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Despite advancement of neural progenitor cell transplantation to spinal cord injury clinical trials, there remains a lack of understanding of how biological sex of transplanted cells influences outcomes after transplantation. To address this, we transplanted GFP-expressing sex-matched, sex-mismatched, or mixed donor cells into sites of spinal cord injury in adult male and female mice. Biological sex of the donor cells does not influence graft neuron density, glial differentiation, formation of the reactive glial cell border, or graft axon outgrowth. However, male grafts in female hosts feature extensive hypervascularization accompanied by increased vascular diameter and perivascular cell density. We show greater T-cell infiltration within male-to-female grafts than other graft types. Together, these findings indicate a biological sex-specific immune response of female mice to male donor cells. Our work suggests that biological sex should be considered in the design of future clinical trials for cell transplantation in human injury.

Date: 2022
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DOI: 10.1038/s41467-022-33134-x

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