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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4182-4188. Prepublished online as a Blood First Edition Paper on January 12, 2006; DOI 10.1182/blood-2005-08-3289.
TRANSPLANTATION Host factors that impact the biodistribution and persistence of multipotent adult progenitor cellsFrom the Pediatric Hematology/Oncology/Blood and Marrow Transplant Program, the Department of Genetics, Cell Biology and Development, and the Stem Cell Institute, University of Minnesota, Minneapolis; the Department of Pediatrics, Stanford University School of Medicine, Stanford, CA; and the Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT.
Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem cells with a broad differentiation potential. We sought to identify factors that affect adoptively transferred MAPCs. In vitro, MAPCs expressed low levels of major histocompatibility complex (MHC) antigens, failed to stimulate CD4+ and CD8+ T-cell alloresponses, and were targets of NK cytolysis. To study in vivo biodistribution, we labeled MAPCs with luciferase for sequential quantification of bioluminescence and DsRed2 for immunohistochemical analysis. C57BL /6 MAPCs were infused intravenously into C57BL /6, Rag-2–/– (T- and B-cell–deficient), and Rag-2–/–/IL-2R
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
c–/– (T-, B-, and NK-cell–deficient) mice. In C57BL /6 mice, MAPCs were transiently detected only in the chest compared with long-term persistence in T- and B-cell–deficient mice. NK depletion reduced MAPC elimination. Because the lungs were the major uptake site after intravenous injection, intra-arterial injections were tested and found to result in more widespread biodistribution. Widespread MAPC biodistribution and long-term persistence were seen in irradiated recipients given allogeneic marrow and MAPCs; such MAPCs expressed MHC class I antigens in tissues. Our data indicate that the biodistribution and persistence of reporter gene–labeled MAPCs are maximized after intra-arterial delivery or host irradiation and that T cells, B cells, and NK cells contribute to in vivo MAPC rejection. 
