Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro.
Exp Cell Res
; 300(1): 65-71, 2004 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-15383315
ABSTRACT
Bone-marrow-derived, circulating endothelial precursor cells contribute to neoangiogenesis in various diseases. Rapamycin has recently been shown to have anti-angiogenic effects in an experimental tumor model. Our group has developed a culture system that allows expansion and endothelial differentiation of human CD133(+) precursor cells. We could show by PCR analysis that mTOR, the rapamycin-binding protein, was expressed in fresh CD133(+) cells, in expanded cells after 28 days, and in differentiated endothelial cells. Rapamycin inhibited proliferation of CD133(+) cells dose dependently at similar concentrations as hematopoietic Jurkat or HL-60 cells. Apoptosis was induced by rapamycin after 48 h of treatment, which could be reduced by preincubation with FK 506. Furthermore, the development of adherent endothelial cells from expanded CD133(+) cells was dose dependently inhibited. Expression of endothelial antigens CD144 and von Willebrand factor on differentiating endothelial precursors was reduced by rapamycin. In summary, rapamycin inhibits proliferation and differentiation of human endothelial precursor cells underlining its anti-angiogenic effects.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Diferenciação Celular
/
Sirolimo
/
Células Endoteliais
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article