组织工程化血管构架及构建环境相关研究与进展

Research and advances in the scaffold and constructing environment of tissue-engineered blood vessel

目的:介绍组织工程血管的支架材料设计、种子细胞的选择及体外动态培养系统的应用现状及进展。资料来源:应用计算机检索PUBMED 1996/2007与组织工程化血管相关的文章,检索词“tissue engineering,vascular,scaffold,seed cell,bioreactor”,限定文献语种为“English”;同时检索万方数据库2000/2007相关文章,检索词“组织工程,血管,支架材料,种子细胞,生物反应器”,限定文献语种为中文。资料选择:共检索到相关文献200余条,选择与组织工程血管构建、组织工程血管支架材料及其生物相容性研究、种子细胞选择相关的文章,无论观察对象为人或动物、无论是否有对照组均纳入,排除综述和重复文献。资料提炼:根据以上标准共纳入30篇进行综述。其中12篇陈述了血管构架材料,12篇介绍种子细胞选择,8篇论述了构建环境对组织工程血管的影响。资料综合:①根据血管构架的来源和性能,可分为天然生物生材料和人工合成材料,因为2种材料均有其缺陷,目前已有研究将天然材料的重要氨基酸序列接在合成聚合物的表面,形成复合生物材料以克服两种材料各自的缺陷。②选取种子细胞的一种途径是从组织活检中直接捕获成熟的血管壁细胞,来源包括自体的非必须大血管壁细胞及微血管壁细胞;另一种途径就是通过构建具有自我更新、多向繁殖分化能力的干细胞工程来获得相应的种子细胞。③组织工程血管的培养环境应尽可能模仿生物体内血管生发的环境条件。结论:到目前为止,组织工程血管的研究主体仍处于实验阶段,现有的临床应用仅仅是少量的尝试性探索。只有从应力与生长关系出发,摸索出能够成功诱导分化成血管壁细胞的干细胞系,在体外完全模拟出新生血管的相同环境,并解决体内移植的组织相容性等问题,才能形成可生长性、可塑形性和高度顺应性的组织工程血管。

OBJECTIVE： To introduce the scaffold material design of tissue-engineered vessel, selection of seed cells and application status and progress in dynamic culture system in vitro. DATA SOURCES： A computer-based online search of PUBMED was undertaken to identify the articles about tissue-engineered vessel published in English from 1996 to 2007 with the key words of ＂tissue engineering, vascular, scaffold, seed cell, bioreactor＂. Meanwhile, we searched the Wanfang Dadabase for related Chinese articles published between 2000 and 2007 with the same key words in Chinese. STUDY SELECTION： More than 200 articles were collected and those about construction of tissue-engineered vessel, scaffold material of tissue-engineered vessel and its biocompatibility, selection of seed cells were selected regardless of human or animals as subjects, control group or not; the review articles and repetitive articles were eliminated. DATA EXTRACTION： Totally 30 articles were selected according to the criteria including 12 about the scaffold material of vessels, 12 about the selection of seed cells, and 8 about the influence of constructing environment on tissue-engineered vessel. DATA SYNTHESIS： （1）Blood vessels could be classified into natural biomaterial and artificial synthetic material according to the source and performance. However, due to their disadvantages, there are some studies about the composite material by connecting the important amino acid sequence of natural matedal to the surface of synthetic polymer to overcome these defects. （2）One approach to select the seed cells is to harvest the mature cells of vascular wall from tissue biopsy, including autogenetic unnecessary cells of great vessel wall and cells of micrangium; the other way is to obtain the seed cells by constructing the stem cells with serf-renewal ability and multi-differentiation potential. （3）The cultivation environment for tissue engineered vessels is better to simulate that of angiogenesis in body. CONCLUSION： So far, the study focus of tissue-engineered vessel is still under exploration, so is the clinical application. Therefore, the tissue-engineered vessels with fissionability, plasticity, and high compliance are obtained only by considering the association of stress and growth, and finding out the stem cell lines that could successfully induce and differentiate into cells of vascular wall.