Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 204, Issue 1, Pages 129-139Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061115
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Funding
- NHLBI NIH HHS [R01 HL058770, R01 HL049997, HL52952, HL49997, HL71228, HL076653, R01 HL063452, HL63452, R01 HL073794, R01 HL052952, HL058770, HL073794, T15 HL076653] Funding Source: Medline
- NIAID NIH HHS [P01 AI 056299, R01 AI047457, AI047457, P01 AI056299] Funding Source: Medline
- NIAMS NIH HHS [T32AR07612, T32 AR050938, T32 AR007612] Funding Source: Medline
- NIDDK NIH HHS [DK5829] Funding Source: Medline
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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.
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