When HSCs are removed from their native environment for the purpose of transplantation, only a small percentage of them find their way to a "home" in the recipient's bone marrow and begin contributing to hematopoiesis. Limiting dilution transplant experiments in adult mice using unfractionated bone marrow has demonstrated that despite the robust engraftment accomplished by bone marrow transplant, ultimately only about 5% to12% of functional adult HSCs transplanted intravenously find their way back to the bone marrow within 24 hours posttrans-plant (Szilvassy et al. 2003). Given this relative inefficiency with which stem cells contribute to engraftment posttransplant, it appears that the unique ability of stem cells to reconstitute long-term hematopoiesis is not due to a special capacity to navigate the vasculature to find the bone marrow, but an ability to adhere to the bone marrow vasculature, extravasate into the bone marrow cavity, and lodge in an hematopoiesis-supporting niche.

Years of transplantation studies and fluorescent-labeling experiments (Papayannopoulou 2003, Lapidot et al. 2005) have demonstrated that transplanted hematopoietic cells are distributed to and deposited in organs throughout the recipient over the first 1 to 3 hours posttransplant, but in less than 48 hours, the transplanted cells are detected almost exclusively in the bone marrow and spleen (Cui et al. 1999, Lanzkron et al. 1999, Srour EF et al. 2001, Szilvassy SJ et al. 2001). Furthermore, although hematopoiesis is initiated in both the spleen and bone marrow, stable engraftment depends on localization of primitive HSC within specialized bone marrow niches. Recent imaging studies point to preferential seeding of quiescent cells to the endosteal regions of the marrow cavity, whereas a combination of quiescent and cycling cells seed the spleen and contribute to radioprotection and short-term engraftment (Nibley and Nibley 1998, Lanzkron et al. 1999, Na Nakorn et al. 2002, Nilsson et al. 2002, Papayannopoulou 2003, Nilsson and Simmons 2004).

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