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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1949-1954.
Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-09-3249.

Submitted September 23, 2003
Accepted October 23, 2003
Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and non-irradiated sites
Hiroshi Ito, Yasuo Takeuchi, Juanita Shaffer, and Megan Sykes*
Transplantation Biology Research Center/Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
* Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu.
Long-term multilineage chimerism is achieved in CD45 congenic mice receiving high bone marrow doses with or without mediastinal irradiation (MI). Increased donor chimerism results in MI-treated compared to unirradiated animals, suggesting that MI makes "space" for engraftment of donor pluripotent hematopoietic stem cells (PHSC). We have now examined whether "space" is systemic, or whether increased engraftment of donor marrow in locally irradiated mice is confined to the irradiated bones. While increased donor chimerism was observed in irradiated bones compared to non-irradiated bones of MI-treated animals 4 weeks following BMT, these differences were minimal by 40 weeks. MI-treated chimeras contained more adoptively transferable donor PHSC in the marrow of both irradiated and distant bones compared to non-MI treated chimeras. Similar proportions of donor PHSC were present in irradiated and non-irradiated bones of locally irradiated mice at both 4 and 40 weeks. Irradiated bones contained more of donor short-term repopulating cells than distant bones at 4 weeks, but not 40 weeks, post-BMT. Our study suggests that local proliferation of donor PHSC in mice receiving local irradiation rapidly leads to a systemic increase in donor PHSC engraftment.

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