Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells
Open Access
- 15 May 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 107 (10), 4182-4188
- https://doi.org/10.1182/blood-2005-08-3289
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.Keywords
This publication has 31 references indexed in Scilit:
- NK CELL RECOGNITIONAnnual Review of Immunology, 2005
- Distinct phases in recovery of reconstituted innate cellular-mediated immunity after murine syngeneic bone marrow transplantationTransplantation and Cellular Therapy, 2004
- Functional roles of NKT cell in the immune systemFrontiers in Bioscience-Landmark, 2004
- Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem CellsScience, 2002
- Pluripotency of mesenchymal stem cells derived from adult marrowNature, 2002
- In vivo developmental stages in murine natural killer cell maturationNature Immunology, 2002
- Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed)Nature Biotechnology, 2002
- Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem CellCell, 2001
- Nonmyeloablative Immunosuppressive Regimen Prolongs In Vivo Persistence of Gene-Modified Autologous T Cells in a Nonhuman Primate ModelJournal of Virology, 2001
- Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized.The Journal of Experimental Medicine, 1987