The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online January 16, 2007
doi:10.1084/jem.20061115
The Journal of Experimental Medicine, Vol. 204, No. 1, 129-139
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Serafini et al.
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ARTICLE

 Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells

Marta Serafini1, Scott J. Dylla3, Masayuki Oki1, Yves Heremans1, Jakub Tolar2, Yuehua Jiang1, Shannon M. Buckley1,4, Beatriz Pelacho1, Terry C. Burns1, Sarah Frommer1, Derrick J. Rossi3, David Bryder3, Angela Panoskaltsis-Mortari2, Matthew J. O'Shaughnessy2, Molly Nelson-Holte1,4, Gabriel C. Fine1, Irving L. Weissman3, Bruce R. Blazar2, and Catherine M. Verfaillie1,4

1 Stem Cell Institute and 2 Cancer Center and Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455
3 Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305
4 Department of Medicine, Stamcel Instituut Leuven, Katholieke Universiteit Leuven, Leuven 3000, Belgium

CORRESPONDENCE Catherine M. Verfaillie: catherine.verfaillie{at}med.kuleuven.be

For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40–80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 103-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs.

Abbreviations used: eGFP, enhanced GFP; ESC, embryonic stem cell; GVHD, graft-versus-host disease; HSC, hematopoietic stem cell; LT-HSC, long-term repopulating HSC; MAPC, multipotent adult progenitor cell; mESC, mouse ESC; NOD, nonobese diabetic; PB, peripheral blood.

M. Serafini and S.J. Dylla contributed equally to this work.


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