Effects of Host/Graft Sex Mismatch on Neural Progenitor Grafts for Spinal Cord Injury
Abstract
Spinal cord injury (SCI) is an extremely devastating injury that can result in complete loss of all motor and sensory functions. Numerous studies have shown transplantation of neural progenitor cells (NPCs) has great promise in restoring lost neural circuitry following SCI. However, little is understood about the biological factors that determine the success of the transplanted graft. One of these potential factors is the role of sex as a biological variable. We sought to determine whether sex mismatch between graft and host tissue influences the survival, differentiation, and integration of transplanted NPCs in a mouse model of SCI. Donor sex was determined for individual GFP+ mouse embryos through rapid genotyping of the X chromosome gene Rbm31x and its divergent Y chromosome gametolog Rbm31y. Either male or female NPCs were then isolated and acutely transplanted into lesion sites of either male or female adult mice. Four weeks following the transplantation, we analyzed neuron and astrocyte differentiation, glial scar formation, and extension of graft-derived axons. Although we did not detect any significant differences in these outcomes, we observed significant hypervascularization in grafts derived from male NPCs within female host animals. This observed vasculature was also associated with abnormally high levels of perivascular density only in this treatment group. Immunohistochemical analysis revealed increased levels of infiltrating immune cells, including leukocytes and lymphocytes, in and around the male-to-female grafts. Altogether, these findings suggest that expression of sex-specific antigens on male donor cells may provoke an inflammatory response in female host animals.
Subject
Spinal cord injuryNeural progenitor cells
Immunology
Stem cell transplantation
Sex as a biological variable
Citation
Pitonak, Michael A (2022). Effects of Host/Graft Sex Mismatch on Neural Progenitor Grafts for Spinal Cord Injury. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /198457.