Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and nonirradiated sites.
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 with nonirradiated animals, suggesting that MI makes "space" for engraftment of donor pluripotent hematopoietic stem cells (PHSCs). 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 with nonirradiated bones of MI-treated animals 4 weeks following bone marrow transplantation (BMT), these differences were minimal by 40 weeks. MI-treated chimeras contained more adoptively transferable donor PHSCs in the marrow of both irradiated and distant bones compared with non-MI-treated chimeras. Similar proportions of donor PHSCs were present in irradiated and nonirradiated bones of locally irradiated mice at both 4 and 40 weeks. Irradiated bones contained more donor short-term repopulating cells than distant bones at 4 weeks, but not 40 weeks, after BMT. Our study suggests that local proliferation of donor PHSCs in mice receiving local irradiation rapidly leads to a systemic increase in donor PHSC engraftment.
Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
Hiroshi
H
Ito
Yasuo
Y
Takeuchi
Juanita
J
Shaffer
Megan
M
Sykes
D019264:Adoptive Transfer; D000483:Alleles; D000818:Animals; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002455:Cell Division; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011827:Radiation; D013045:Species Specificity; D013997:Time Factors
D015704:CD4 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens