Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells

Chengcheng Zhang, Megan Kaba, Guangtao Ge, Kathleen Xie, Wei Tong, Christopher Hug, Harvey F. Lodish

Research output: Contribution to journalArticle

262 Scopus citations

Abstract

Successful ex vivo expansion of hematopoietic stem cells (HSCs) would greatly benefit the treatment of disease and the understanding of crucial questions of stem cell biology. Here we show, using microarray studies, that the HSC-supportive mouse fetal liver CD3+ cells specifically express the proteins angiopoietin-like 2 (Angptl2) and angiopoietin-like 3 (Angptl3). We observed a 24- or 30-fold net expansion of long-term HSCs by reconstitution analysis when we cultured highly enriched HSCs for 10 days in the presence of Angptl2 or Angptl3 together with saturating levels of other growth factors. The coiled-coil domain of Angptl2 was capable of stimulating expansion of HSCs. Furthermore, angiopoietin-like 5, angiopoietin-like 7 and microfibril-associated glycoprotein 4 also supported expansion of HSCs in culture.

Original languageEnglish (US)
Pages (from-to)240-245
Number of pages6
JournalNature medicine
Volume12
Issue number2
DOIs
StatePublished - Mar 14 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Zhang, C., Kaba, M., Ge, G., Xie, K., Tong, W., Hug, C., & Lodish, H. F. (2006). Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells. Nature medicine, 12(2), 240-245. https://doi.org/10.1038/nm1342