Prolongation of cardiac allograft survival by a novel population of autologous CD117+ bone marrow-derived progenitor cells.
Autologous CD117(+) progenitor cells (PC) have been successfully utilized in myocardial infarction and ischemic injury, potentially through the replacement/repair of damaged vascular endothelium. To date, such cells have not been used to enhance solid organ transplant outcome. In this study, we determined whether autologous bone marrow-derived CD117(+) PC could benefit cardiac allograft survival, possibly by replacing donor vascular cells. Autologous, positively selected CD117(+) PC were administered posttransplantation and allografts were assessed for acute rejection. Although significant generation of recipient vascular cell chimerism was not observed, transferred PC disseminated both to the allograft and to peripheral lymphoid tissues and facilitated a significant, dose-dependent prolongation of allograft survival. While CD117(+) PC dramatically inhibited alloreactive T cell proliferation in vitro, this property did not differ from nonprotective CD117(-) bone marrow populations. In vivo, CD117(+) PC did not significantly inhibit T cell alloreactivity or increase peripheral regulatory T cell numbers. Thus, rather than inhibiting adaptive immunity to the allograft, CD117(+) PC may play a cytoprotective role in prolonging graft survival. Importantly, autologous CD117(+) PC appear to be distinct from bone marrow-derived mesenchymal stem cells (MSC) previously used to prolong allograft survival. As such, autologous CD117(+) PC represent a novel cellular therapy for promoting allograft survival.
Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA. Todd.Grazia@ucdenver.edu
T J
TJ
Grazia
R J
RJ
Plenter
H M
HM
Lepper
F
F
Victorino
S D
SD
Miyamoto
J T
JT
Crossno
B A
BA
Pietra
R G
RG
Gill
M R
MR
Zamora
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D019009:Proto-Oncogene Proteins c-kit