Insulin-like growth factor-binding protein 2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells

HoangDinh Huynh, Satoru Iizuka, Megan Kaba, Oktay Kirak, Junke Zheng, Harvey F. Lodish, Chengcheng Zhang

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1628-1635
Number of pages8
JournalSTEM CELLS
Volume26
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Cell culture
  • Cytokines
  • Ex vivo expansion
  • Flow cytometry
  • Growth factors
  • Hematopoietic stem cell transplantation
  • Hematopoietic stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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