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使用 GRGDSPC 肽改善脱细胞胰腺支架的再内皮化。

Using GRGDSPC peptides to improve re-endothelialization of decellularized pancreatic scaffolds.

机构信息

Center for Difficult and Complicated Abdominal Surgery, The Tenth Hospital Affiliated Shanghai Tongji University, Shanghai, China.

Department of General Surgery, Affiliated Hospital of Nantong University, Nan Tong, China.

出版信息

Artif Organs. 2020 Apr;44(4):E172-E180. doi: 10.1111/aor.13602. Epub 2019 Dec 15.

DOI:10.1111/aor.13602
PMID:31736099
Abstract

Engineering of functional vascularized pancreatic tissues offers an alternative way to solve the perpetual shortage of organs for transplantation. However, revascularization remains a major bottleneck in biological engineering, which limited the further clinical applications of this strategy. In this study, an efficient approach for enhancing re-endothelialization of rat decellularized pancreatic scaffolds (DPS) was presented, by conjugating with GRGDSPC peptide to maximize coverage of the vessel walls with human umbilical vein endothelial cells (HUVECs). First, pancreas was perfused with 1% Triton X-100 and 0.1% ammonium hydroxide to remove the cellular components. Subsequently, GRGDSPC was covalently coupled to the vasculature of DPS and re-seeded with HUVECs via perfusion of the portal vein in the bioreactor. After the re-endothelialized scaffolds were created, in vitro and in vivo experiments were undertaken to evaluate the angiogenesis. Our results demonstrated that GRGDSPC-conjugated scaffolds could support the survival and accelerated the proliferation of HUVECs; angiogenesis was also significantly improved over untreated scaffolds. In conclusion, GRGDSPC-conjugated scaffolds showed great potential for the generation of functional bioengineered pancreatic tissue suitable for long-term transplantation.

摘要

工程化功能性血管化胰腺组织为解决器官移植的永久性短缺提供了一种替代方法。然而,再血管化仍然是生物工程中的一个主要瓶颈,限制了该策略的进一步临床应用。在这项研究中,通过与 GRGDSPC 肽缀合,最大限度地覆盖血管壁上的人脐静脉内皮细胞(HUVEC),提出了一种增强大鼠脱细胞胰腺支架(DPS)再内皮化的有效方法。首先,用 1% Triton X-100 和 0.1%氨水溶液灌注胰腺,以去除细胞成分。然后,GRGDSPC 通过生物反应器中的门静脉灌注与 DPS 的脉管系统共价偶联,并重新接种 HUVEC。在创建再内皮化支架后,进行了体外和体内实验来评估血管生成。我们的结果表明,GRGDSPC 缀合的支架可以支持 HUVEC 的存活和加速增殖;与未处理的支架相比,血管生成也得到了显著改善。总之,GRGDSPC 缀合的支架为生成适合长期移植的功能性生物工程胰腺组织提供了巨大潜力。

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