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猪脱细胞真皮基质与人脐静脉内皮细胞构建组织工程中的功能性新血管生成。

Functional neovascularization in tissue engineering with porcine acellular dermal matrix and human umbilical vein endothelial cells.

机构信息

Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, China.

出版信息

Tissue Eng Part C Methods. 2011 Apr;17(4):423-33. doi: 10.1089/ten.TEC.2010.0466. Epub 2010 Dec 19.

DOI:10.1089/ten.TEC.2010.0466
PMID:21062229
Abstract

Endothelial cells-matrix interactions play an important role in promoting and controlling network formation. In this study, porcine acellular dermal matrix (PADM) was used to guide human umbilical vein endothelial cells (HUVECs) adhesion and proliferation as a potential system for vascularization of engineered tissues. We fabricated PADM using a modified protocol and assessed their composition and ultrastructures. Subsequently, the viability of HUVECs and the formation of capillary-like networks were evaluated by seeding cells directly on PADM scaffolds or PADM digests in vitro. We further investigated the function of the HUVECs seeded on the PADM scaffolds after subcutaneous transplantation in athymic mice. Moreover, the function of the neovessels formed in the PADM scaffolds was assessed by implantation into cutaneous wounds on the backs of mice. The results showed that PADM scaffolds significantly increased proliferation of HUVECs, and the PADM digest induced HUVECs formed many tube-like structures. Moreover, HUVECs seeded on the PADM scaffolds formed numerous capillary-like networks and some perfused vascular structures after implantation into mice. PADM seeded with HUVECs and fibroblasts were also able to form many capillary-like networks in vitro. Further, these neovessels could inosculate with the murine vasculature after implantation into cutaneous wounds in mice. The advantage of this method is that the decellularized matrix not only provides signals to maintain the viability of endothelial cells but also serves as the template structure for regenerated tissue. These findings indicate that PADM seeded with HUVECs may be a potential system for successful engineering of large, thick, and complex tissues.

摘要

内皮细胞-基质相互作用在促进和控制网络形成中起着重要作用。在这项研究中,使用猪去细胞真皮基质(PADM)作为引导人脐静脉内皮细胞(HUVEC)黏附和增殖的潜在系统,用于工程化组织的血管化。我们使用改良的方案制造 PADM,并评估其组成和超微结构。随后,通过将细胞直接接种在 PADM 支架或 PADM 消化物上,在体外评估 HUVEC 的活力和毛细血管样网络的形成。我们进一步研究了 HUVEC 接种在无胸腺鼠皮下后的 PADM 支架上的功能。此外,通过将 PADM 支架植入小鼠背部的皮肤伤口来评估新形成的血管的功能。结果表明,PADM 支架显著增加了 HUVEC 的增殖,而 PADM 消化物诱导 HUVEC 形成了许多管状结构。此外,将 HUVEC 接种在 PADM 支架上后,植入小鼠体内可形成许多毛细血管样网络和一些灌注的血管结构。接种 HUVEC 和成纤维细胞的 PADM 也能够在体外形成许多毛细血管样网络。此外,这些新血管在植入小鼠皮肤伤口后可以与鼠血管吻合。该方法的优点是脱细胞基质不仅提供了维持内皮细胞活力的信号,而且还作为再生组织的模板结构。这些发现表明,接种 HUVEC 的 PADM 可能是成功构建大型、厚壁和复杂组织的潜在系统。

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