PMID- 28100035 OWN - NLM STAT- MEDLINE DCOM- 20180122 LR - 20181202 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 35 IP - 5 DP - 2017 May TI - Stromal Cells Act as Guardians for Endothelial Progenitors by Reducing Their Immunogenicity After Co-Transplantation. PG - 1233-1245 LID - 10.1002/stem.2573 [doi] AB - 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 stem/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 leukocyte antigen (HLA)-mismatched human peripheral blood mononuclear cells (PBMCs). In vitro, cell surface marker changes due to interferon gamma (IFNgamma) stimulation during ECFC/MSC coculture were determined and further effects on allostimulated T cell proliferation and cytotoxic lysis were measured. IFNgamma-induced HLA-DR expression on ECFCs and MSCs, but both cell types had significantly less HLA-DR in cocultures. ECFC-induced T cell proliferation was abolished after MSC coculture as a result of HLA-DR downregulation and indolamin-2,3-dioxygenase activation. Additionally, allospecific CD8(+) T cell-mediated lysis of ECFCs was reduced in cocultures. ECFC/MSC coapplication in immunodeficient mice not only promoted the generation of improved blood vessel architecture after 6 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 coapplication for therapeutic vasculogenesis. Stem Cells 2017;35:1233-1245. CI - (c) 2017 AlphaMed Press. FAU - Souidi, Naima AU - Souidi N AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. FAU - Stolk, Meaghan AU - Stolk M AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. FAU - Rudeck, Juliane AU - Rudeck J AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. FAU - Strunk, Dirk AU - Strunk D AD - Institute of Experimental and Clinical Cell Therapy, Paracelsus Medical University, Salzburg, Austria. AD - Spinal Cord & Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. FAU - Schallmoser, Katharina AU - Schallmoser K AD - Spinal Cord & Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria. AD - Department for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University, Salzburg, Austria. FAU - Volk, Hans-Dieter AU - Volk HD AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. FAU - Seifert, Martina AU - Seifert M AD - Institute of Medical Immunology, Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. AD - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. LA - eng PT - Journal Article DEP - 20170223 PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (HLA-DR Antigens) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/cytology/drug effects MH - Cell Proliferation/drug effects MH - Coculture Techniques MH - Colony-Forming Units Assay MH - Cytotoxicity, Immunologic/drug effects MH - Down-Regulation/drug effects MH - Endothelial Cells/cytology/drug effects/*immunology/*transplantation MH - Female MH - HLA-DR Antigens/metabolism MH - Humans MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism MH - Inflammation/pathology MH - Interferon-gamma/pharmacology MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Neovascularization, Physiologic/drug effects MH - Stromal Cells/cytology/drug effects/transplantation OTO - NOTNLM OT - Cell transplantation OT - Endothelial progenitor cells OT - Histocompatibility antigens OT - Immunomodulation OT - Neovascularization OT - Stromal cells EDAT- 2017/01/19 06:00 MHDA- 2018/01/23 06:00 CRDT- 2017/01/19 06:00 PHST- 2016/07/29 00:00 [received] PHST- 2016/12/07 00:00 [revised] PHST- 2016/12/18 00:00 [accepted] PHST- 2017/01/19 06:00 [pubmed] PHST- 2018/01/23 06:00 [medline] PHST- 2017/01/19 06:00 [entrez] AID - 10.1002/stem.2573 [doi] PST - ppublish SO - Stem Cells. 2017 May;35(5):1233-1245. doi: 10.1002/stem.2573. Epub 2017 Feb 23.