Journal
BLOOD
Volume 107, Issue 10, Pages 4182-4188Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-08-3289
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Funding
- NCRR NIH HHS [1S10 RR 16851] Funding Source: Medline
- NHLBI NIH HHS [R01 HL 49997, R01 HL 55209, R01 HL 52952] Funding Source: Medline
- NICHD NIH HHS [5K12 HD 033692] Funding Source: Medline
- NIDDK NIH HHS [DK 49022] Funding Source: Medline
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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 gamma(-/-)(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.
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