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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.
Previous Article | Next Article 
Submitted August 12, 2005
Accepted January 5, 2006
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 S McIvor, Stephen R Yant, Mark A Kay, Diane Krause, Catherine M Verfaillie, and Bruce R Blazar
Pediatrics, Hematology-Oncology, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA
Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA
Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA
Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA
* Corresponding author; email: tolar003{at}umn.edu.
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 MHC antigens, failed to stimulate CD4+ and CD8+ T cell alloresponses, and were targets of NK cytolysis. To study in vivo biodistibution, MAPCs were labeled 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 c-/- (T-, B- and NK-deficient) mice. In C57BL/6 mice, MAPCs were transiently detected only in the chest compared to long-term persistence in T- and B- cell deficient mice. NK depletion reduced MAPC elimination. Since the lungs were the major uptake site after intravenous injection, intra-aterial injections were tested and found to result in a more widespread biodistribution. Widespread MAPC biodistribution and long-term persistence was 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 is maximized after intra-arterial delivery or host irradiation and indicate that T- and/or B-cells as well as NK cells contribute to in vivo MAPC rejection.

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