Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal strem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo. Immunodeficient mice received subcutaneous grafts containing human ECFCs alone, or pairs of human ECFCs/MSCs from the same umbilical cord (UC) to study vasculogenesis in the presence of human leucocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNγ) stimulation during ECFC/MSC co-culture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNγ induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in co-cultures. ECFC-induced T cell proliferation was abolished after MSC co-culture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase (IDO) activation. Additionally, allospecific CD8(+) T cell-mediated lysis of ECFCs was reduced in co-cultures. ECFC/MSC co-application in immunodeficient mice not only promoted the generation of improved blood vessel architecture after six weeks, but also reduced intragraft immune cell infiltration and endothelial HLA-DR expression following PBMC reconstitution. Crosstalk between UC-derived ECFCs and MSCs after combined transplantation can lower the risk of ECFC rejection, thus enabling their co-application for therapeutic vasculogenesis. This article is protected by copyright. All rights reserved.
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