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

• Published in: Blood 2006-05, Vol.107 (10), p.4182-4188
• Main Authors: Tolar, Jakub, O'Shaughnessy, Matthew J., Panoskaltsis-Mortari, Angela, McElmurry, Ron T., Bell, Scott, Riddle, Megan, McIvor, R. Scott, Yant, Stephen R., Kay, Mark A., Krause, Diane, Verfaillie, Catherine M., Blazar, Bruce R.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Survival; Killer Cells, Natural - immunology; Lymphocyte Culture Test, Mixed; Lymphocyte Depletion; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Stem Cell Transplantation; Stem Cells - cytology; Stem Cells - immunology; T-Lymphocytes - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Whole-Body Irradiation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-08-3289

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.