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用于骨修复的组织工程支架中血管生成的诱导:一种联合基因治疗-细胞移植方法。

Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

作者信息

Jabbarzadeh Ehsan, Starnes Trevor, Khan Yusuf M, Jiang Tao, Wirtel Anthony J, Deng Meng, Lv Qing, Nair Lakshmi S, Doty Steven B, Laurencin Cato T

机构信息

Departments of Orthopaedic Surgery and Chemical Engineering, University of Virginia, Charlottesville, VA 22908, USA.

出版信息

Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11099-104. doi: 10.1073/pnas.0800069105. Epub 2008 Aug 4.

Abstract

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.

摘要

组织工程方法的一个基本原则是新形成的组织必须保持足够的血管化以支持其生长。最近,诱导血管长入组织工程支架的努力致力于开发新策略,以递送特定的生物因子,这些生物因子可引导内皮细胞(EC)祖细胞的募集及其分化。然而,挑战在于细胞、合适的生物因子和最佳因子剂量的协调。本研究报告了一种通过结合体外基因转移策略和EC移植来解决这一困境的方法。通过使用用于骨组织工程应用的3D聚(丙交酯-共-乙交酯)(PLAGA)烧结微球支架评估了该方法的效用。我们的目标是通过用编码VEGF cDNA的腺病毒分离和转染脂肪来源的基质细胞(ADSCs)来实现的。我们证明,释放VEGF的ADSCs和ECs的组合导致PLAGA支架内显著的血管生长。我们从而描绘了ADSCs促进血管长入生物材料的潜力。

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