Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
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.
Serafini
Marta
M
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.
Dylla
Scott J
SJ
Oki
Masayuki
M
Heremans
Yves
Y
Tolar
Jakub
J
Jiang
Yuehua
Y
Buckley
Shannon M
SM
Pelacho
Beatriz
B
Burns
Terry C
TC
Frommer
Sarah
S
Rossi
Derrick J
DJ
Bryder
David
D
Panoskaltsis-Mortari
Angela
A
O'Shaughnessy
Matthew J
MJ
Nelson-Holte
Molly
M
Fine
Gabriel C
GC
Weissman
Irving L
IL
Blazar
Bruce R
BR
Verfaillie
Catherine M
CM
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
D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins