Analyzing the Immunobiology of Cultured Mesenchymal Stromal Cells

Abstract

Mesenchymal stromal cells (MSC) are known to possess both immuno-privileged and immuno-inhibitory properties, thereby widening their therapeutic potential. Ex vivo expansion is necessary to obtain sufficient numbers for therapy. Despite suggestions that ex vivo expansion might alter MSC biology, there is no systematic study that delineates changes in MSC immunobiology during extended culture. We have investigated this systematically. Our results show that the immuno-privileged and immuno-suppressive properties of MSC diminished with increasing passage number during in vitro culture. The reduction of MSC immuno-inhibitory properties was associated with a concomitant increase in their immunogenicity. Our results show that the immuno-modulatory cytokines, TGF-beta and IL-10, contributed to these effects but did not account for all as other in vivo soluble MSC molecules inhibited delayed-type hypersensitivity in a paracrine or endocrine manner. The suppression of lymphocyte migration is probably involved in the immuno-inhibitory activity of MSC in vivo. These data may account for the low efficacy of allogeneic tissue regeneration and inconsistent observations in MSC-based immune therapy. Hence, this study provides a theoretical basis for prolonging the effects and improving the efficacy of allogeneic MSC in cellular therapy by implanting MSC at early passage numbers combined with choosing a better administration method.