Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine.
Our laboratory has previously reported a nonmyelosuppressive preparative regimen for hematopoietic cell transplantation that leads to mixed chimerism and allograft tolerance in miniature swine across minor and major histocompatibility disparities. Stable chimerism persisted in most of these animals but was restricted to T cells and confined to peripheral blood. Because of the importance of myeloid and erythroid progenitors for the treatment of hematologic disorders, the objective of this study was to assess whether such cells existed in the bone marrow of these lymphoid chimeras as an indication of functional engraftment. Colony-formation assays were performed on donor inocula before infusion and on bone marrow cells harvested from the transplant recipients. Donor-origin myeloid/erythroid progenitor colonies were detected in bone marrow from 6 of 7 lymphoid chimeric recipients. A delayed donor leukocyte infusion successfully converted a stable lymphoid chimera to full multilineage chimerism within 2 weeks. Donor-origin myeloid/erythroid progenitors could be detected in the bone marrow of a host-matched recipient after myeloablation and adoptive transfer of mobilized cells from one of the engrafted lymphoid chimeras. These data suggest that even when only lymphoid chimerism is readily detected by flow cytometry, dormant myeloid/erythroid progenitors can exist and subsequent conversion to full donor chimerism can be achieved. The ability to establish multilineage engraftment and chimerism without significant toxicity may have important clinical implications for the management of nonmalignant hematopoietic disorders and hematologic malignancies.
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D017252:CD3 Complex / Q000032:analysis; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000737:chemistry; D005434:Flow Cytometry; D006098:Granulocytes / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II; D007377:Interleukin-3 / Q000494:pharmacology; D007937:Leukapheresis; D008214:Lymphocytes / Q000737:chemistry; D009000:Monocytes / Q000737:chemistry; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D023461:Myeloid Progenitor Cells / Q000737:chemistry; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D016133:Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000254:growth & development* / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D023001:Transplantation Tolerance / Q000276:immunology*
D015703:Antigens, CD; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007377:Interleukin-3; D019089:Stem Cell Factor; C438668:swine leukocyte antigen