Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long-term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice.
Mobilized peripheral blood progenitor cells (PBPC) have been shown to provide rapid engraftment in patients given high-dose chemotherapy. PBPC contain cells with long-term engraftment potential as shown in animal models. In this study we have further analyzed mobilized PBPC for their ability to support serial transplantation of irradiated mice. Transplantation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PBPC resulted in 98% donor engraftment of primary recipients at 12 to 14 months post-transplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients had donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes. Myeloid colonies from BM cells of secondary recipients demonstrated granulocyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resulted in decreased male engraftment in secondary recipients. BM cells from secondary recipients, who originally received PBPC mobilized by the combination of rrSCF and rhG-CSF, were further passaged to tertiary female recipients. At 6 months posttransplantation, 90% of animals had male-derived hematopoiesis by whole-blood PCR analysis. These data showed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that are transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem cells (LTRC) have extensive proliferative potential and resemble those that reside in the BM. In addition, the data demonstrated increased mobilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone.
Yan
X Q
XQ
Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA 91320-1789, USA.
Hartley
C
C
McElroy
P
P
Chang
A
A
McCrea
C
C
McNiece
I
I
D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002455:Cell Division; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016133:Polymerase Chain Reaction; D011828:Radiation Chimera; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D013997:Time Factors; D014998:Y Chromosome
D016298:Hematopoietic Cell Growth Factors; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor