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Proc Natl Acad Sci U S A ; 105(32): 11099-104, 2008 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-18678895

RESUMO

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.


Assuntos
Adipócitos/metabolismo , Diferenciação Celular , Células Endoteliais/metabolismo , Terapia Genética , Neovascularização Fisiológica , Transplante de Células-Tronco , Células-Tronco/metabolismo , Engenharia Tecidual , Adenoviridae , Adipócitos/citologia , Adipócitos/transplante , Tecido Adiposo/metabolismo , Tecido Adiposo/ultraestrutura , Regeneração Óssea/genética , Diferenciação Celular/genética , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/ultraestrutura , Terapia Genética/métodos , Humanos , Ácido Láctico/química , Microesferas , Neovascularização Fisiológica/genética , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células-Tronco/ultraestrutura , Células Estromais/metabolismo , Células Estromais/ultraestrutura , Engenharia Tecidual/métodos , Transfecção , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
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