中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (1): 120-127.doi: 10.12307/2025.021

• 干细胞综述 stem cell review • 上一篇    下一篇

干细胞在小口径人工血管内皮化中的应用

郑安垲,刘瑞明,向秋玲   

  1. 中山大学中山医学院,广东省广州市   510080
  • 收稿日期:2023-11-17 接受日期:2023-12-22 出版日期:2025-01-08 发布日期:2024-05-18
  • 通讯作者: 向秋玲,女,教授,博士生导师,中山大学中山医学院,广东省广州市 510080
  • 作者简介:郑安垲,男,2003年生,广东省东莞市人,汉族,中山大学中山医学院临床医学(本博连读)在读,主要从事小口径人工血管研究。
  • 基金资助:
    国家自然科学基金面上项目(82272164),项目负责人:向秋玲;广东省自然科学基金(2021A1515011648),项目负责人:向秋玲

Application of stem cells in endothelialization of small-diameter blood vessel prosthesis

Zheng Ankai, Liu Ruiming, Xiang Qiuling   

  1. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
  • Received:2023-11-17 Accepted:2023-12-22 Online:2025-01-08 Published:2024-05-18
  • Contact: Xiang Qiuling, Professor, Doctoral supervisor, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
  • About author:Zheng Ankai, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
  • Supported by:
    Xiang Qiuling, Professor, Doctoral supervisor, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China

摘要:

文题释义:
小口径人工血管:是一种直径在6 mm以下的、由人工合成材料或天然材料制备成的、可替代病变血管的管形植入物。
内皮化:通过材料表面改性促进细胞黏附或体外种植细胞等方法,使人工血管内表面覆盖细胞,发挥类似天然内皮的生理功能。


背景:小口径人工血管移植后由于血栓形成和内膜增生等原因造成管腔狭窄甚至闭塞,运用干细胞作为种子细胞实现人工血管的内皮化有助于改善血管移植后的远期通畅率。
目的:总结干细胞在小口径人工血管内皮化中应用的研究进展。
方法:由第一作者检索PubMed和万方数据库2013-2023年发表的相关文献,英文检索词为“vascular graft,tissue-engineered blood vessel/vascular tissue engineering,endothelialization,stem cells,endothelial progenitor cells,mesenchymal stem cells,induced pluripotent stem cells,embryonic stem cells”,中文检索词为“人工血管,组织工程血管/血管组织工程,内皮化,干细胞,内皮祖细胞,间充质干细胞,诱导多能干细胞,胚胎干细胞”,检索近10年国内外关于干细胞应用于小口径人工血管内皮化的相关文献,初检文献552篇,根据纳排标准最终选取81篇文献进行综述。
结果与结论:①远期通畅率不理想限制了小口径人工血管的临床应用,造成远期通畅率低下的主要原因是血栓形成和内膜增生。天然血管内皮层具有良好的抗血栓及内膜增生性能,内皮化可以模拟天然血管的特性,是提升远期通畅率的有效手段。②小口径人工血管植入体内后会经历体内内皮化过程,但难以形成完整的内皮层。干细胞具有分化为内皮细胞的潜能,体内招募干细胞或将其作为种子细胞种植在人工血管内表面是实现内皮化的研究策略。③将内皮祖细胞、间充质干细胞、诱导多能干细胞及胚胎干细胞等作为种子细胞种植均能够一定程度改善小口径人工血管的远期通畅率,且它们各具优势。内皮祖细胞便于获取且可直接用于种植;间充质干细胞来源广泛且具有旁分泌和调节免疫的功能;诱导多能干细胞来源丰富且可消除免疫原性;胚胎干细胞增殖能力强且能多向分化。④将干细胞用于人工血管的研究目前仍未转化至临床,未来需要进一步研究并促进临床转化。

https://orcid.org/0009-0007-8517-8519 (郑安垲) 

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 小口径人工血管, 内皮化, 干细胞, 内皮祖细胞, 间充质干细胞, 诱导多能干细胞, 胚胎干细胞, 综述

Abstract: BACKGROUND: The small-diameter blood vessel prosthesis faces the problem of lumen stenosis or even occlusion due to thrombogenesis and intimal hyperplasia after transplantation. The application of stem cells as seed cells to achieve endothelialization of blood vessel prosthesis helps to improve the long-term patency rate after vascular graft transplantation.
OBJECTIVE: To summarize the research progress of the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis.
METHODS: The relevant articles published on PubMed and WanFang databases from 2013 to 2023 were retrieved by the first author. Chinese and English search terms included “vascular graft, tissue-engineered blood vessel/vascular tissue engineering, endothelialization, stem cells, endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, embryonic stem cells.” The relative articles in the domestic and overseas about the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis in the past 10 years were retrieved. A total of 552 articles were initially found and we finally selected 81 articles to review according to inclusion and exclusion criteria. 
RESULTS AND CONCLUSION: (1) The low long-term patency rate restricts the application of small-diameter blood vessel prosthesis in clinic. The main causes of low long-term patency rate are thrombogenesis and intimal hyperplasia. The endothelium of native vessels has the function of anti-thrombogenesis and intimal hyperplasia. Endothelialization can simulate the function of native vessels, which is an effective way to improve long-term patency rate. (2) The small-diameter blood vessel prosthesis will undergo in vivo endothelialization after being implanted, but it is difficult to form complete endothelium. Stem cells have the potential to differentiate into endothelial cells. Recruiting stem cells in vivo or seeding them on the inner surface of blood vessel prosthesis in vitro is research strategy to achieve endothelialization. (3) The long-term patency rate of small-diameter blood vessel prosthesis has been improved to a certain extent through seeding endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells. Each has its own advantages. Endothelial progenitor cells are easy to obtain and can be directly used for seeding. Mesenchymal stem cells come from a wide range of sources and have the function of paracrine and immunological regulation. Induced pluripotent stem cells are rich in sources and the immunogenicity can be eliminated. Embryonic stem cells have a strong proliferative ability and can differentiate into many cells. (4) The application of stem cells in blood vessel prosthesis has not yet been transformed into clinic. Further researches are needed to promote clinical translation.

Key words: small-diameter blood vessel prosthesis, endothelialization, stem cell, endothelial progenitor cell, mesenchymal stem cell, induced pluripotent stem cell, embryonic stem cell, review

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