期刊
STEM CELLS
卷 26, 期 6, 页码 1628-1635出版社
ALPHAMED PRESS
DOI: 10.1634/stemcells.2008-0064
关键词
ex vivo expansion; hematopoietic stem cells; cell culture; cytokines; flow cytometry; growth factors; hematopoietic stem cell transplantation
资金
- NCI NIH HHS [K01-CA120099-01, K01 CA120099, K01 CA120099-01] Funding Source: Medline
- NIDDK NIH HHS [R01-DK067356, R01 DK067356] Funding Source: Medline
Successful hematopoietic stem cell (HSC) transplantation is often limited by the numbers of HSCs, and robust methods to expand HSCs ex vivo are needed. We previously showed that angiopoietin-like proteins (Angptls), a group of growth factors isolated from a fetal liver HSC-supportive cell population, improved ex vivo expansion of HSCs. Here, we demonstrate that insulin-like growth factor-binding protein 2 (IGFBP2), secreted by a tumorigenic cell line, also enhanced ex vivo expansion of mouse HSCs. On the basis of these findings, we established a completely defined, serum-free culture system for mouse HSCs, containing SCF, thrombopoietin, fibroblast growth factor 1, Angptl3, and IGFBP2. As measured by competitive repopulation analyses, there was a 48-fold increase in numbers of long-term repopulating mouse HSCs after 21 days of culture. This is the first demonstration that IGFBP2 stimulates expansion or proliferation of murine stem cells. Our finding also suggests that certain cancer cells synthesize proteins that can stimulate HSC expansion.
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