Engraftment of Embryonic Stem Cells and Differentiated Progeny by Host Conditioning with Total Lymphoid Irradiation and Regulatory T Cells

•ESCs and differentiated progeny are readily rejected in immunocompetent animals•TLI, ATS, and Treg are used to induce engraftment of allogeneic ESC transplantation•TLI and ATS promote the engraftment of ESC and differentiated progeny allografts•TLI plus Treg promote the engraftment of ESC and differentiated progeny allografts

SummaryEmbryonic stem cells (ESCs) hold promise for the treatment of many medical conditions; however, their utility is limited by immune rejection. The objective of our study is to establish tolerance or promote engraftment of transplanted ESCs as well as mature cell populations derived from ESCs. Luciferase (luc+)-expressing ESCs were utilized to monitor the survival of the ESCs and differentiated progeny in living recipients. Allogeneic recipients conditioned with fractioned total lymphoid irradiation (TLI) and anti-thymocyte serum (ATS) or TLI plus regulatory T cells (Treg) promoted engraftment of ESC allografts after transplantation. Following these treatments, the engraftment of transplanted terminally differentiated endothelial cells derived from ESCs was also significantly enhanced. Our findings provide clinically translatable strategies of inducing tolerance to adoptively transferred ESCs for cell replacement therapy of medical disorders.

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