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Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells

Author(s)
Chou, Song; Flygare, Johan; Lodish, Harvey F.
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Abstract
We have developed a coculture system that establishes DLK[superscript +] fetal hepatic progenitors as the authentic supportive cells for expansion of hematopoietic stem (HSCs) and progenitor cells. In 1-week cultures supplemented with serum and supportive cytokines, both cocultured DLK[superscript +] fetal hepatic progenitors and their conditioned medium supported rapid expansion of hematopoietic progenitors and a small increase in HSC numbers. In 2- and 3-week cultures DLK[superscript +] cells, but not their conditioned medium, continuously and significantly (>20-fold) expanded both hematopoietic stem and progenitor cells. Physical contact between HSCs and DLK[superscript +] cells was crucial to maintaining this long-term expansion. Similar HSC expansion (approximately sevenfold) was achieved in cocultures using a serum-free, low cytokine- containing medium. In contrast, DLK[superscript -] cells are incapable of expanding hematopoietic cells, demonstrating that hepatic progenitors are the principle supportive cells for HSC expansion in the fetal liver.
Date issued
2013-02
URI
http://hdl.handle.net/1721.1/102178
Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Journal
Experimental Hematology
Publisher
Elsevier
Citation
Chou, Song, Johan Flygare, and Harvey F. Lodish. “Fetal Hepatic Progenitors Support Long-Term Expansion of Hematopoietic Stem Cells.” Experimental Hematology 41, no. 5 (May 2013): 479–490.e4.
Version: Author's final manuscript
ISSN
0301472X

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