title: Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
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 10(3)-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.
authors.affiliation: Stem Cell Institute and Cancer Center and Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Serafini
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Dylla
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oki
authors.forename: Yves
authors.initials: Y
authors.lastname: Heremans
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Buckley
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.forename: Terry C
authors.initials: TC
authors.lastname: Burns
authors.forename: Sarah
authors.initials: S
authors.lastname: Frommer
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: O'Shaughnessy
authors.forename: Molly
authors.initials: M
authors.lastname: Nelson-Holte
authors.forename: Gabriel C
authors.initials: GC
authors.lastname: Fine
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000235:genetics; D006410:Hematopoiesis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006413:Hematopoietic System / Q000166:cytology; D066298:In Vitro Techniques; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000276:immunology / Q000637:transplantation*; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins