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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
XQ Yan, C Hartley, P McElroy, A Chang, C McCrea and I McNiece
Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA
91320-1789, USA.
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.
Volume 85,
Issue 9,
pp. 2303-2307,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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