Fetal hepatic progenitors support long-term expansion of hematopoietic stem cells
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Lodish_Fetal hepatic.pdf
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Author(s) • •
Chou, Song
Flygare, Johan
Lodish, Harvey F
Date Issued
February 2013
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.
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Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1016/j.exphem.2013.02.003