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 PROLIFERATIONFOR MORE THAN 2 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. PB PC contain cells with long-term engraftment potential as shown in anim al models. In this study we have further analyzed mobilized PBPC for t heir ability to support serial transplantation of irradiated mice. Tra nsplantation of recombinant human granulocyte colony-stimulating facto r (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PB PC resulted in 98% donor engraftment of primary recipients at 12 to 14 months posttransplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients h ad donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes, Mye loid colonies from BM cells of secondary recipients demonstrated granu locyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resu lted in decreased male engraftment in secondary recipients, BM cells f rom secondary recipients, who originally received PBPC mobilized by th e 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 wholeblood PCR analysis. These data sho wed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that a re transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem ce lls (LTRC) have extensive proliferative potential and resemble those t hat reside in the BM. In addition, the data demonstrated increased mob ilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone. ( C) 1995 by The American Society of Hematology.