Nature Medicine
- 12, 240 - 245 (2006)
Published online: 22 January 2006; | doi:10.1038/nm1342
Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cellsCheng Cheng Zhang1, Megan Kaba1, Guangtao Ge1, Kathleen Xie1, Wei Tong1, Christopher Hug1, 2, 3 & Harvey F Lodish1, 41
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA. 2
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. 3
Division of Respiratory Diseases, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. 4
Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Harvey F Lodish lodish@wi.mit.edu 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.
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