Improved vascular organization enhances functional integration of engineered skeletal muscle grafts
Improved vascular organization enhances functional integration of engineered skeletal muscle grafts
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DOI：
10.1073/pnas.1017825108
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发表时间：
2011-09-06
影响因子：
11.1
通讯作者：
Levenberg, Shulamit
中科院分区：
文献类型：
--
作者：
Koffler, Jacob;Kaufman-Francis, Keren;Levenberg, Shulamit
严重的创伤事件，如烧伤和癌症治疗，往往涉及大量的组织损失，需要通过自体肌肉瓣的手术重建。高质量带血管瓣的可用性不足和供区发病率往往限制了它们的使用。工程化血管移植为这一需求提供了另一种选择。这项工作描述了体外血管化和组织组织程度的首次分析，需要提高体内血管化肌肉移植物整合的速度和效率。虽然一天的体外培养足以使移植物整合，但三周的培养期可以产生半组织的血管结构和肌肉纤维，显著提高移植效果。植入血管网络逐渐被宿主血管取代，同时灌注和毛细血管密度增强。移植物血管生成关键因子的上调提示其在促进血管生成反应中起积极作用。从卫星细胞到成熟纤维的转变表明基因表达增加，毛细血管与纤维的比例增加，形态与正常肌肉相似。我们建议采用“接力”方法，延长体外培养时间，形成更有结构的血管床，允许移植物-宿主血管生成协作，促进吻合和血管整合。增强的血管生成反应支持增强的肌肉再生、成熟和整合。
Severe traumatic events such as burns, and cancer therapy, often involve a significant loss of tissue, requiring surgical reconstruction by means of autologous muscle flaps. The scant availability of quality vascularized flaps and donor site morbidity often limit their use. Engineered vascularized grafts provide an alternative for this need. This work describes a first-time analysis, of the degree of in vitro vascularization and tissue organization, required to enhance the pace and efficacy of vascularized muscle graft integration in vivo. While one-day in vitro was sufficient for graft integration, a three-week culturing period, yielding semiorganized vessel structures and muscle fibers, significantly improved grafting efficacy. Implanted vessel networks were gradually replaced by host vessels, coupled with enhanced perfusion and capillary density. Upregulation of key graft angiogenic factors suggest its active role in promoting the angiogenic response. Transition from satellite cells to mature fibers was indicated by increased gene expression, increased capillary to fiber ratio, and similar morphology to normal muscle. We suggest a "relay" approach in which extended in vitro incubation, enabling the formation of a more structured vascular bed, allows for graft-host angiogenic collaboration that promotes anastomosis and vascular integration. The enhanced angiogenic response supports enhanced muscle regeneration, maturation, and integration.