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首页> 外文期刊>Tissue Engineering Part A >In Vivo Pulmonary Tissue Engineering: Contribution of Donor-Derived Endothelial Cells to Construct Vascularization*
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In Vivo Pulmonary Tissue Engineering: Contribution of Donor-Derived Endothelial Cells to Construct Vascularization*

机译：体内肺组织工程：供体来源的内皮细胞对构建血管化的贡献*

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摘要

Intrapulmonary engraftment of engineered lung tissues could provide a potential therapeutic approach for the treatment of pediatric and adult pulmonary diseases. In working toward this goal, we report here on in vivo generation of vascularized pulmonary tissue constructs utilizing the subcutaneous Matrigel plug model. Mixed populations of murine fetal pulmonary cells (FPCs) containing epithelial, mesenchymal, and endothelial cells (ECs) were isolated from the lungs of embryonic day 17.5 fetuses. FPCs were admixed to Matrigel and injected subcutaneously into the anterior abdominal wall of adult C57/BL6 mice to facilitate in vivo pulmonary tissue construct formation. Vascularization was enhanced by placing fibroblast growth factor 2 (FGF2)–loaded polyvinyl sponges into the hydrogel. After 1 week, routine histology and immunohistochemical staining for donor-derived epithelial cells and ECs as well as analysis of patent vasculature in the constructs following tail vein injection of fluorescein isothiocyanate–conjugated dextran were performed. In the Matrigel-only controls, some level of host infiltrate, but no measurable vascularization, was detected. In the presence of FPCs, the constructs contained ductal epithelial structures and patent vasculature. In the absence of FPCs, exogenous FGF2 induced the formation of numerous patent blood vessels throughout the entire constructs; in combination with FPCs, it resulted in enhanced capillary density and abundant interfacing between developing epithelial and vascular structures. The significant findings of this study are that distal pulmonary epithelial differentiation (as assessed by the expression of prosurfactant protein C) can be maintained in vivo and that donor-derived ECs contribute to the formation of patent vessels that interface tightly with ductal epithelial structures.
机译：工程肺组织的肺内植入可以为儿童和成人肺部疾病的治疗提供潜在的治疗方法。为了实现这一目标，我们在此报告了利用皮下基质胶模型在体内生成血管化肺组织的过程。从胚胎第17.5天胎儿的肺中分离出含有上皮，间质和内皮细胞（EC）的鼠胎儿肺细胞（FPC）的混合种群。将FPC与Matrigel混合并皮下注射到成年C57 / BL6小鼠的前腹壁中，以促进体内肺组织构建物的形成。通过将载有成纤维细胞生长因子2（FGF2）的聚乙烯海绵放入水凝胶中，可以增强血管化作用。 1周后，对尾静脉注射异硫氰酸荧光素-缀合的葡聚糖，对供体来源的上皮细胞和EC进行常规组织学和免疫组织化学染色，并对构建物中的专利脉管系统进行分析。在仅Matrigel的对照中，检测到一定水平的宿主浸润，但未检测到可测的血管形成。在存在FPC的情况下，构建体包含导管上皮结构和专利脉管系统。在没有FPC的情况下，外源性FGF2诱导了整个构建体中大量专利血管的形成。与FPCs结合使用，可增强毛细血管密度，并在发育中的上皮和血管结构之间形成丰富的界面。这项研究的重要发现是，可以在体内维持远端肺上皮细胞的分化（通过表面活性剂蛋白C的表达进行评估），并且源自供体的EC有助于形成与导管上皮结构紧密接触的专利血管。

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  • 来源
    《Tissue Engineering Part A》 |2008年第3期|361-368|共8页
  • 作者

    Mark J. Mondrinos; Sirma H. Koutzaki; Honesto M. Poblete; M. Cecilia Crisanti; Peter I. Lelkes; Christine M. Finck;

  • 作者单位

    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania.;

    Department of Pediatric Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania.;

    Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania.;

    Department of Pediatric Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania.;

    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania.;

    Department of Pediatric Surgery, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania.|Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania.|Current address: Department of Pediatric Surgery, Connecticut Children's Hospital, Hartford, Connecticut.;

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