Development of mesenchymal stem cell homing

doi:10.3969/j.issn.2095-4344.2016.19.021

Abstract

Abstract:

BACKGROUND: As a kind of adult stem cells with low immunogenicity, mesenchymal stem cells are able to differentiate into different cell lineages in the treatment of many diseases. Moreover, mesenchymal stem cells have been extensively used in many fields such as stem cell transplantation, immune therapy, and tissue engineering.
OBJECTIVE: To review the progress of homing mechanism and the strategies to promote mesenchymal stem cell homing, thus providing a theoretical basis for transplanting mesenchymal stem cells safely and efficiently.
METHODS: The CNKI and PubMed databases were retrieved by computer for articles regarding mesenchymal stem cell homing published from 2000 to 2016, including reviews, basic and clinical studies. The key words were “mesenchymal stem cells, homing” in Chinese and English, respectively. Then 74 papers were suitable for final analysis.
RESULTS AND CONCLUSION: Mesenchymal stem cell homing needs further research, especially the molecular mechanism of cell mobilization. Therefore, basic research about mesenchymal stem cells should be further developed, and a standardized homing system should be established in vitro. In addition, it is of great significance to study the in vivo effects of transplanted gene-transfected mesenchymal stem cells.

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

Key words: Mesenchymal Stem Cells, Chemotactic Factors, Tissue Engineering

CLC Number:

R318

Deng Rong-rong, Xie Yi-min, Xie Lin. Development of mesenchymal stem cell homing[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(19): 2879-2888.

Figures/Tables 1

2.1 间充质干细胞的生物学特性间充质干细胞是一类具有自我更新、高度增殖、免疫调控、造血支持及多向分化潜能的非造血干细胞，最早在骨髓中发现[1]，随后在多种组织中发现，如脂肪、脐带沃顿胶、脐血等[2-3]。目前国际公认的人间充质干细胞表型特征为：细胞表面CD73、CD90、CD105等抗原呈阳性，而CD14、CD79a、CD11b、CD19、CD34、CD45、HLA-DR等表达阴性[4]。大多数人类间充质干细胞可以作为中胚层组织如骨骼、脂肪和软骨发育的前体细胞，同时还可以跨越胚层横向分化为各种组织细胞[5-7]，如神经细胞和内皮细胞等[8]。间充质干细胞是一类低免疫原性的成体干细胞，间充质干细胞的低免疫原性与其低表达主要组织相容性复合体MHC-Ⅰ而不表达MHC-Ⅱ、CD40、CD80、CD86有关，同时间充质干细胞对各类免疫细胞均具有免疫调节作用。研究发现间充质干细胞可通过调节T细胞的活化和增殖来抑制免疫反应[9-10]。间充质干细胞对T细胞的调节可通过细胞间直接接触[11-12]，亦可在非直接接触下间充质干细胞分泌可溶性因子来发挥作用。内源性间充质干细胞可产生相应的生长因子和细胞因子在组织修复过程中发生作用，如骨形态发生蛋白在骨、肌腱、软骨的修复中发挥作用[13]，促血管再生因子可用于缺血性疾病的治疗。基因修饰的干细胞移植是目前临床研究的热点，因此，间充质干细胞的低免疫原性及促进机体修复的特点使其成为备受关注的可用于移植的干细胞之一，而移植的间充质干细胞能否顺利归巢至微环境，是决定间充质干细胞移植的成败之一。 2.2 间充质干细胞的归巢及归巢机制干细胞归巢是指自体或外源性干细胞在多种因素的作用下，能定向趋向性迁移，越过血管内皮细胞至靶向组织并定植存活的过程，类似人体局部炎症反应后大量白细胞迁移至炎症周围，见图2。2009年Krap等[14]建议将“间充质干细胞归巢”定义为：间充质干细胞在目标组织的脉管系统里被捕获，随后跨越血管内皮细胞迁移至目标组织的过程。间充质干细胞与血管内皮细胞具有相似性，因而易于迁移和植入。干细胞“巢”作为一种特殊的微环境，是干细胞存在的基础，“巢”通过不同信号途径调控着干细胞的行为，使干细胞的生长、更新和分化在生理条件下处于稳定平衡状态。对于归巢机制，尤其是干细胞的动员，目前无法准确的阐述。大部分研究文献基于白细胞迁移、人类干细胞以及转移肿瘤细胞研究干细胞的迁移行为，针对各种细胞表面受体及细胞因子进行探索。"

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