Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells

Jakub Tolar, Matthew J. O'Shaughnessy, Angela Panoskaltsis-Mortari, Ron T. McElmurry, Scott Bell, Megan Riddle, R. Scott McIvor, Stephen R. Yant, Mark A. Kay, Diane Krause, Catherine M. Verfaillie, Bruce R. Blazar

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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-2Rγc-/- (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.

Original languageEnglish (US)
Pages (from-to)4182-4188
Number of pages7
JournalBlood
Volume107
Issue number10
DOIs
StatePublished - May 15 2006

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