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Blood, 1 July 2002, Vol. 100, No. 1, pp. 312-317
TRANSPLANTATION
Growth factor treatment prior to low-dose total body irradiation
increases donor cell engraftment after bone marrow transplantation
in mice
Estelle J. K. Noach,
Albertina Ausema,
Jan H. Dillingh,
Bert Dontje,
Ellen Weersing,
Imre Akkerman,
Edo Vellenga, and
Gerald de Haan
From the Department of Stem Cell Biology, University of
Groningen and Division of Hematology, University Hospital Groningen,
Groningen, The Netherlands.
Low-toxicity conditioning regimens prior to bone marrow
transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that
treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or
7 days with growth factors (stem cell factor [SCF] plus interleukin
11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed
in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL.
Although 1-day pretreatments with these cytokines initially resulted in
reduced donor cell engraftment, a continuous increase in time was
observed, finally resulting in highly significantly increased levels of
donor cell contribution. In contrast, G-CSF treatment showed no
beneficial effects on long-term engraftment. In vitro stem cell assays
demonstrated the effect of cytokine treatment on stem cell numbers.
Donor cell engraftment and number of remaining recipient stem cells
after TBI were strongly inversely correlated, except for groups treated
for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that
long-term donor cell engraftment can be strongly augmented by treatment
of recipient mice prior to low-dose TBI with hematopoietic growth
factors that act on primitive cells.
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C. Barese, N. Pech, S. Dirscherl, J. L. Meyers, A. L. Sinn, M. C. Yoder, W. S. Goebel, and M. C. Dinauer
Granulocyte Colony-Stimulating Factor Prior to Nonmyeloablative Irradiation Decreases Murine Host Hematopoietic Stem Cell Function and Increases Engraftment of Donor Marrow Cells
Stem Cells,
June 1, 2007;
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1578 - 1585.
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