Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells.
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.
Zhang
Cheng Cheng
CC
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Kaba
Megan
M
Ge
Guangtao
G
Xie
Kathleen
K
Tong
Wei
W
Hug
Christopher
C
Lodish
Harvey F
HF
D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D001798:Blood Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins