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

Marta Serafini, Scott J. Dylla, Masayuki Oki, Yves Heremans, Jakub Tolar, Yuehua Jiang, Shannon M. Buckley, Beatriz Pelacho, Terry C. Burns, Sarah Frommer, Derrick J. Rossi, David Bryder, Angela Panoskaltsis-Mortari, Matthew J. O'Shaughnessy, Molly Nelson-Holte, Gabriel C. Fine, Irving L. Weissman, Bruce R. Blazar, Catherine M. Verfaillie

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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. JEM

Original languageEnglish (US)
Pages (from-to)129-139
Number of pages11
JournalJournal of Experimental Medicine
Volume204
Issue number1
DOIs
StatePublished - Jan 22 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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