中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (21): 3424-3430.doi: 10.3969/j.issn.2095-4344.0489

• 干细胞综述 stem cell review • 上一篇    下一篇

软骨组织工程中脂肪干细胞：标记物、基因修饰及与支架的理想结合

魏一凡1，2，曾 静1，2，张 巍3，王 尧1，2，陈犹白1，韩 岩1   

  1. 1解放军总医院整形修复科，北京市 100853；2南开大学医学院，天津市 300071；3解放军总医院骨科，北京市 100853
  • 修回日期:2018-02-07 出版日期:2018-07-28 发布日期:2018-07-28
  • 通讯作者: 陈犹白，博士，主治医师，讲师，解放军总医院整形修复科，北京市 100853
  • 作者简介:魏一凡，女，1992年生，河北省廊坊市人，汉族，南开大学医学院在读硕士，医师。
  • 基金资助:

    国家自然科学基金面上项目(81272123)

Adipose-derived stem cells in cartilage tissue engineering: cell markers, genetic modifications, and the ideal combination with scaffolds

Wei Yi-fan1, 2, Zeng Jing1, 2, Zhang Wei3, Wang Yao1, 2, Chen You-bai1, Han Yan1   

  1. 1Department of Plastic Surgery, 3Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, China; 2Medical School of Nankai University, Tianjin 300071, China
  • Revised:2018-02-07 Online:2018-07-28 Published:2018-07-28
  • Contact: Chen You-bai, M.D., Attending physician, Lecturer, Department of Plastic Surgery, General Hospital of Chinese PLA, Beijing 100853, China
  • About author:Wei Yi-fan, Master candidate, Physician, Department of Plastic Surgery, General Hospital of Chinese PLA, Beijing 100853, China; Medical School of Nankai University, Tianjin 300071, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81272123

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摘要：

文章快速阅读：

文题释义：
软骨组织工程种子细胞：理想的种子细胞应具有来源丰富、易于提取、对供区的损伤小、表型稳定、支架材料黏附率高、增殖力强、无明显免疫排斥反应等特点。目前软骨组织工程的种子细胞主要有软骨细胞、胚胎干细胞、骨髓干细胞、脐带干细胞、脂肪干细胞等。
脂肪干细胞：脂肪干细胞是来源于脂肪组织，具有自我更新和多向分化潜能的间充质干细胞，体外培养可贴壁生长，表达CD29，CD44，CD73，CD90和CD105，不表达CD14，CD31，CD45和CD235a，可作为多种组织工程的种子细胞。

 

摘要
背景：软骨损伤和缺损一直以来是困扰骨科和整形科医师的难题，组织工程为修复软骨缺损提供了新的途径。脂肪干细胞的来源充足、提取容易、损伤低、产量高、分离简单、增殖力强、具有多向分化潜能，因此成为软骨组织工程种子细胞的热门选择。
目的：文章分析利用脂肪干细胞构建组织工程软骨的影响因素，总结验证脂肪干细胞向软骨细胞分化的方法，讨论构建组织工程软骨的主要瓶颈，并展望利用组织工程手段修复软骨缺损的研究方向。
方法：于2017年6月5日在PubMed数据库中以“(((adipose stem cell[Title]) OR adipose-derived stem cell[Title]) OR adipose-derived mesenchymal stem cell[Title]) AND chondrogenic differentiation[Title]”作为检索式检索。于2017年8月4日在SinoMed中以“("脂肪干细胞"[中文标题：智能]) AND "软骨"[中文标题：智能]”作为检索式检索。通过标题及摘要选取与脂肪干细胞的向软骨细胞分化相关的文献，并阅读其参考文献的标题和摘要，从中再次选取与脂肪干细胞向软骨细胞分化相关的文献，剔除重复文献。
结果与结论：检索符合条件文献35篇，其中近5年文献30篇。SinoMed中符合条件文献71篇，综述9篇，近5年文献22篇。最终纳入文献60篇。转化生长因子β、骨形态发生蛋白及胰岛素样生长因子等均可促进脂肪干细胞向软骨细胞分化，多种生长因子联合应用或将生长因子基因转染入脂肪干细胞，实现长效稳定缓释，是目前的研究热点之一。传统的地塞米松、胰岛素及维生素C，配合几种生长因子的成软骨分化诱导配方仍然是目前的主流诱导方法。利用细胞共培养、微球、支架、动态三维培养，均可有效提高组织工程软骨的构建效率和质量，但是寻找一种理想的支架材料依然是目前的主要问题。此外，细胞来源、培养条件、miRNA、富血小板血清及甲状旁腺素相关肽等也可影响脂肪干细胞向软骨细胞分化。除了细胞形态的改变之外，利用染色或对Sox9、Ⅱ型胶原蛋白、硫酸软骨素及硫酸角质素等软骨特异性基因和蛋白的检测，是验证脂肪干细胞分化为软骨细胞的可靠手段。未来的研究方向集中在寻找脂肪干细胞的特异性标记物，决定外源性生长因子联合应用的顺序和剂量，利用基因修饰种子细胞以及构建理想的支架材料上。

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
ORCID: 0000-0002-3616-8548(魏一凡)

关键词: 脂肪干细胞, 种子细胞, 成软骨分化, 软骨形成, 软骨组织工程, 转化生长因子, 骨形态发生蛋白, 胰岛素样生长因子, 化学药物, 细胞微环境, 干细胞移植

Abstract:

BACKGROUND: Cartilage injury and defect have always been a challenge to orthopedic and plastic surgeons. Tissue engineering technology provides a novel promising approach to repair cartilage defects. Adipose-derived stem cells (ADSCs) are a great source of seed cells for cartilage tissue engineering due to the sufficient storage, easy harvest, high yield, easy isolation, strong proliferation and multilineage differentiation capability.
OBJECTIVE: To analyze the factors that influence the construction of tissue-engineered cartilage using ADSCs as seed cells, to summarize the methods that verify a successful differentiation towards chondrocytes from ADSCs, to discuss some issues on the ADSCs based cartilage tissue engineering, and to look forward the future of cartilage tissue engineering.
METHODS: On June 5, 2017, we searched in PubMed using the following strategy “(((adipose stem cell[Title]) OR adipose-derived stem cell[Title]) OR adipose-derived mesenchymal stem cell[Title]) AND chondrogenic differentiation[Title]”. On August 4, 2017, we searched in SinoMed using the following strategy “(“adipose-derived stem cell”[Title]) AND “cartilage”[Title]” in Chinese. We first selected literatures related to ADSC differentiation into chondrocyte or cartilage tissue engineering using ADSCs as seed cells according to their titles and abstracts. We then read the titles of the references of the selected literatures and reselected the articles associated with the same topic from the references and removed the repetitive literatures.
RESULTS AND CONCLUSION: There were 35 eligible literatures in PubMed, among which 30 were published in recent 5 years. There were 71 eligible literatures in SinoMed, among which 9 were reviews and 22 were published in recent 5 years. Finally, 60 literatures were included for this review. Growth factors such as transforming growth factor β, bone morphogenetic protein, insulin-like growth factor can facilitate the ADSCs differentiation towards chondrocytes. The combination of several growth factors and gene modification of ADSCs utilizing the above-mentioned growth factor genes for a long-term stable release are in the spotlight of current research. Traditional induction medium recipe consisting of dexamethasone, insulin, vitamin C and several growth factors is still the mainstream in the current market. Cell culture methods such as coculture, microsphere, scaffold, and dynamic three-dimensional culturing system can promote the efficiency and quality of the construction of tissue engineered cartilage. However it is essential to find an ideal scaffold material. Furthermore, other factors including ADSCs source, culture conditions, miRNA, platelet rich plasma, parathyroid hormone related peptides can also affect the ADSCs differentiation towards chondrocytes. Besides the morphological changes of induced ADSCs, the chondrogenic differentiation can also be verified through dyeing or the detection of specific genes and proteins such as Sox9, Collagen II, chondroitin sulfate, and keratansulfate. The future research interest will focus on the specific marker of ADSCs, the sequence and dose of exogenous growth factors for combined utility, gene-modified ADSCs and scaffold materials.

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: Stem Cells, Tissue Engineering, Cartilage

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