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PMID: 17227908 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 204 ·No. 1 ·2007-01-22 ·Pages 129-39

Serafini M, Dylla SJ, Oki M, Heremans Y, Tolar J, Jiang Y, Buckley SM, Pelacho B, Burns TC, Frommer S, Rossi DJ, Bryder D, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Nelson-Holte M, Fine GC, Weissman IL, Blazar BR, Verfaillie CM

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.

MeSH Terms
Animals B-Lymphocytes/immunology Graft Survival Green Fluorescent Proteins/genetics Hematopoiesis/immunology Hematopoietic Stem Cell Transplantation Hematopoietic System/cytology In Vitro Techniques Lymphoid Tissue/cytology Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Mice, Transgenic Multipotent Stem Cells/immunology,transplantation Organ Specificity Recombinant Proteins/genetics T-Lymphocytes/immunology
Chemicals
Recombinant Proteins Green Fluorescent Proteins
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Serafini Marta
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
Oki Masayuki
Heremans Yves
Tolar Jakub
Jiang Yuehua
Buckley Shannon M
Pelacho Beatriz
Burns Terry C
Frommer Sarah
Rossi Derrick J
Bryder David
Panoskaltsis-Mortari Angela
O'Shaughnessy Matthew J
Nelson-Holte Molly
Fine Gabriel C
Weissman Irving L
Blazar Bruce R
Verfaillie Catherine M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20061115
Published
2007-01-22
Epub
2007-00-16
Pages
129-39
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118428
Subset
IM
Grants
NHLBI NIH HHS · HL63452 · United States
NHLBI NIH HHS · R01 HL073794 · United States
NHLBI NIH HHS · R01 HL052952 · United States
NHLBI NIH HHS · T15 HL076653 · United States
NHLBI NIH HHS · HL073794 · United States
NIAID NIH HHS · P01 AI056299 · United States
NIAMS NIH HHS · T32AR07612 · United States
NIAID NIH HHS · P01 AI 056299 · United States
NHLBI NIH HHS · HL058770 · United States
NIAMS NIH HHS · T32 AR007612 · United States
NHLBI NIH HHS · HL49997 · United States
NIDDK NIH HHS · DK5829 · United States
NHLBI NIH HHS · HL52952 · United States
NIAMS NIH HHS · T32 AR050938 · United States
NHLBI NIH HHS · R01 HL063452 · United States
NIAID NIH HHS · R01 AI047457 · United States
NHLBI NIH HHS · HL71228 · United States
NIAID NIH HHS · AI047457 · United States
NHLBI NIH HHS · HL076653 · United States
NHLBI NIH HHS · R01 HL049997 · United States
NHLBI NIH HHS · R01 HL058770 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1084/jem.20061115 PMC Full Text View journal details
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