Angiopoietin-like Proteins Stimulate Ex Vivo Expansion of Hematopoietic Stem Cells

Nat Med. 2006 Feb;12(2):240-5. doi: 10.1038/nm1342. Epub 2006 Jan 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiopoietin-like Proteins
  • Angiopoietins / genetics
  • Angiopoietins / metabolism
  • Angiopoietins / pharmacology*
  • Animals
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Blood Proteins / pharmacology
  • Cell Line
  • Hematopoiesis / drug effects
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Transfection

Substances

  • Angiopoietin-like Proteins
  • Angiopoietins
  • Angptl2 protein, mouse
  • Blood Proteins
  • Intercellular Signaling Peptides and Proteins
  • Recombinant Proteins