“Neutral Allografts” Cultured Allogeneic Cells as Building Blocks of Engineered Organs Transplanted Across MHC Barriers

Abstract

To avoid the rejection of an allograft by the host, it is commonly thought that there is a need to match donor and host or to manipulate in some way either the allograft or the host immune system. Prolonged in vitro culture of organ allografts prior to transplantation may lead to a diminished rejection response (Jacobs, 1974, Lafferty et al., 1976, Lacy et al., 1990). This outcome could be due to the modification of alloantigenicity (Lafferty et al., 1976) or loss of passenger leukocytes from the graft (Lafferty et al., 1983). Neonatal tissues have been allografted without rejection, thus differentiating between antigenicity and immunogenicity in neonatal and adult tissues (Demidem et al., 1990). The immunogenic elements of an allograft have generally been thought to be cells of hematopoietic origin or small vessel endothelium rather than its parenchymal or mesenchymal cells (Dvorak et al., 1980, Faustman et al., 1984, Demidem et al., 1986). This opens the possibility of allografting cultured cells, potentially, but not necessarily of neonatal origin.