Engraftment of post 5-fluorouracil murine marrow into minimally myeloablated (100 cGy) murine hosts.
(2002) Journal of Hematotherapy & Stem Cell Research — Vol. 11, n° 3, p. 483-490 (2002)
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- Minimal myeloablative approaches are now being widely applied in the treatment of different hematological malignancies. One hundred cGy whole-body irradiation is a stem-cell-toxic, relatively non-myelotoxic treatment that allows for relatively high levels of donor chimerism. 5-Fluorouracil (5-FU) treatment leads to a relative concentration of high proliferative potential-colony-forming cell (HPP-CFC) and is an approach that has been used to induce in vivo progenitor/stem cell cycling to facilitate retroviral integration in gene therapy approaches. We have now evaluated the capacity of marrow harvested 1, 2, 6, or 12 days after 5-FU treatment (150 mg/kg) to engraft in 100 cGy-treated female BALB/c mice. Engraftment was assessed at 3, 10, and 24 weeks. A rapid induction of an engraftment defect occurred 1 day post 5-FU and persisted through day 6 with a recovery by day 12. To evaluate cell cycle status of normal and 5-FU-treated marrow cells, male donors received hydroxyurea (900 mg/kg i.v.) or phosphate-buffered saline (PBS), 2 h prior to marrow harvest and transplantation into submyeloablated female recipients. Engraftment levels were similar for hydroxyurea-treated mice and controls. Thus, these studies show transiently defective engraftment of 5-FU-treated marrow into submyeloablated hosts, which may be related to the cell cycle status of the stem cells.
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D’Hondt, L., Lambert, J.-F., Damon, J., Benoit, B. O., Cerny, J., Carlson, J. E., Reilly, J., Wuu, J., Colvin, G. A., Dooner, M. S., & Quesenberry, P. J. (2002). Engraftment of post 5-fluorouracil murine marrow into minimally myeloablated (100 cGy) murine hosts. Journal of Hematotherapy & Stem Cell Research, 11(3), 483-490. https://doi.org/10.1089/15258160260090942 (Original work published 2002)