Facilitating cells enable engraftment of purified fetal liver stem cells in allogeneic recipients.
It has been reported that while stem cells purified from adult bone marrow engraft in syngeneic recipients, they fail to engraft in allogeneic recipients. We have recently shown that the addition of as few as 30,000 facilitating cells (CD8+/CD3+/CD45R+/Thy 1.2+/TCR-), a unique bone marrow-derived population that does not possess stem cell properties, results in the permanent engraftment of stem cells in a major histocompatibility complex (MHC)-disparate allogeneic host. It has been suggested that fetal hematopoietic tissue may be a source of stem cells with enhanced proliferative and self-renewal properties compared with adult bone marrow. We were interested, therefore, in whether fetal stem cells demonstrated a superior capacity to engraft in allogeneic recipients. In this study, we have examined the engraftment properties of mouse fetal liver cells in syngeneic and allogeneic recipients. Transplantation of unmodified fetal liver cells into allogeneic recipients results in stable multilineage chimerism with donor-specific tolerance, indicating that the pluripotent hematopoietic stem cell is present in fetal liver and is capable of engraftment in allogeneic adult recipients. Similarly, 2000 to 3000 sorted fetal liver stem cells (Sca+/c-kit+/Lin-) successfully reconstituted lethally irradiated syngeneic adults and adults differing only in minor histocompatibility antigens. Two thousand to 10,000 fetal stem cells failed to rescue lethally irradiated allogeneic recipients, but the addition of 30,000 MHC-matched purified facilitating cells to the fetal stem cell inoculum resulted in sustained engraftment with multilineage production. These results, which parallel our earlier work with stem cells derived from adult bone marrow, indicate that the pluripotent fetal stem cell behaves in a fashion similar to that of adult stem cells with regard to allogeneic transplantation.
Gaines
B A
BA
Division of Cellular Therapeutics, Department of Surgery, University of Pittsburgh, PA 15261, USA.
Colson
Y L
YL
Kaufman
C L
CL
Ildstad
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D002678:Chimera; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D005333:Fetus; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006649:Histocompatibility Antigens / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D015778:Minor Histocompatibility Antigens