Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells.
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-2Rgamma(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.
Tolar
Jakub
J
Pediatric Hematology/Oncology/Blood and Marrow Transplantation Program, MMC 366, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA. tolar003@umn.edu
O'shaughnessy
Matthew J
MJ
Panoskaltsis-Mortari
Angela
A
McElmurry
Ron T
RT
Bell
Scott
S
Riddle
Megan
M
McIvor
R Scott
RS
Yant
Stephen R
SR
Kay
Mark A
MA
Krause
Diane
D
Verfaillie
Catherine M
CM
Blazar
Bruce R
BR
D000818:Animals; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation