Comparison of the Growth and Fate of Fetal Spinal Iso- and Allografts in the Adult Rat Injured Spinal Cord

Abstract

Most studies investigating early fetal CNS graft–host interactions and host immune responses have been performed using intracerebral transplantation paradigms. The purpose of this study was to establish the early developmental dynamics of fetal graft integration with the injured host spinal cord and to determine whether fetal allografts in this environment are subject to rejection. ACI rat fetal spinal cord (FSC) tissue was grafted into acute lesion cavities of adult WF rat spinal cords. Graft development and/or rejection was followed from 1 to 45 days posttransplantation with morphometric, histological, and immunocytochemical methods. We determined that all FSC grafts in acute resection lesions of the adult rat spinal cord undergo an early substantial cellular attrition, but following favorable attachment to healthy host tissue margins, they rebound and grow to fill the lesion cavity by approximately 45 days. We also determined that FSC allografts into nonimmunosuppressed adult recipients are consistently rejected, but only after an early period of growth and maturation. The onset of rejection is characterized by extensive cellular infiltration coincidental with graft and host MHC antigen expression. The implications of delayed graft development and graft–host integration are discussed relative to interconnectivity and long-term potential for graft-derived benefits. The observed rejection response was characteristic of first-order allograft rejection and underscores a lack of immunological privilege in the microenvironment of the injured spinal cord.