中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (1): 126-132.doi: 10.3969/j.issn.2095-4344.0422

• 干细胞综述 stem cell review • 上一篇    下一篇

脂肪干细胞成肌分化及修复骨骼肌损伤：应用现状及未来研究方向

陈犹白1，2，张 巍3，栗 利1，张启旭2，韩 岩1   

  1. 1解放军总医院整形修复科，北京市 100853；2美国德克萨斯大学MD安德森肿瘤中心整形外科，美国休斯敦 77030；3解放军总医院骨科，北京市 100853
  • 修回日期:2017-08-13 出版日期:2018-01-08 发布日期:2018-01-08
  • 通讯作者: 韩岩，主任医师，教授，博士生导师，解放军总医院整形修复科，北京市 100853； 并列通讯作者：张启旭，副教授，美国德克萨斯大学MD安德森肿瘤中心整形外科，休斯敦 77030
  • 作者简介:陈犹白，男，1986年生，黑龙江省齐齐哈尔市人，汉族，2016年解放军医学院毕业，博士，主治医师，主要从事脂肪干细胞和组织工程研究。

Adipose-derived stem cells: current progress and future perspectives regarding the myogenic differentiation and use in the repair of skeletal muscle defects

Chen You-bai1, 2, Zhang Wei3, Li Li1, Zhang Qi-xu2, Han Yan1   

  1. 1Department of Plastic and Reconstructive Surgery, 3Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, China; 2Department of Plastic Surgery, University of Texas MD Anderson Cancer Center, Texas, USA)
  • Revised:2017-08-13 Online:2018-01-08 Published:2018-01-08
  • Contact: Han Yan, Chief physician, Professor, Doctoral supervisor, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China;Zhang Qi-xu, Associate professor, Department of Plastic Surgery, University of Texas MD Anderson Cancer Center, Texas, USA
  • About author:Chen You-bai, M.D., Attending physician, Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China; Department of Plastic Surgery, University of Texas MD Anderson Cancer Center, Texas, USA

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摘要：

文章快速阅读：

文题释义：
MyoD：是成肌分化的主要调节因子和开关基因，其在静止的肌肉卫星细胞中不表达，但是在肌肉损伤后开始表达，因此，MyoD是鉴定肌肉修复和再生的标记物。MyoD对肌肉卫星细胞的影响是剂量依赖性的，高水平的MyoD抑制细胞再生，促进终末分化，诱发凋亡。MyoD通过与靶基因的启动子区或增强子区的一致性保守序列E-box相结合，激活肌肉特异性基因的转录，促进成肌分化。
脱细胞肌肉组织支架：利用物理和化学方法，去除肌肉组织中的细胞成分，保留了细胞外基质及各种生长因子，这种脱细胞支架保留了肌肉组织原有的三维结构，具有较强的力学性能，为种子细胞的附着、增殖和分化提供了有力的条件。

 

摘要
背景：骨骼肌再生能力较低，一旦缺损后治疗手段有限，是困扰整形科和骨科医师的难题。脂肪干细胞来源充足，获取简便，产量高，增殖能力强，能旁分泌各种细胞因子，在特定条件下可分化为骨骼肌成肌细胞。基于脂肪干细胞的细胞疗法和肌肉组织工程为骨骼肌损伤的修复提供了新的思路。
目的：总结脂肪干细胞向骨骼肌成肌细胞分化的过程，分析影响脂肪干细胞成肌分化的因素和机制，讨论脂肪干细胞的肿瘤安全性及限制其临床应用的主要瓶颈。
方法：于2017年6月10日在PubMed中以“((myogenic[Title]) OR myogenesis[Title]) AND adipose stem cell[MeSH Terms]”作为检索式检索，在SinoMed中以“(((“脂肪”[标题：智能]) AND“干细胞”[标题：智能]) AND “肌”[标题：智能]) AND “分化”[标题：智能]”作为检索式检索。在所有检索文献中，纳入脂肪干细胞向骨骼肌分化或修复骨骼肌损伤的相关文献，并从其参考文献中再次筛选，排除重复文献。
结果与结论：PubMed中符合条件的文献47篇，其中近5年文献26篇。SinoMed中符合条件的文献47篇，其中脂肪干细胞向心肌细胞分化34篇，向平滑肌分化6篇，剩余文章7篇。最终纳入中英文文献共50篇。脂肪干细胞在定向诱导下向骨骼肌成肌细胞分化是多种基因、蛋白和信号通路交互作用的复杂过程。除传统的化学诱导外，利用条件培养基或与肌细胞共培养也可促进脂肪干细胞向骨骼肌成肌细胞分化。化学元素、生物力学因素、成肌调节因子、生长因子、microRNA及某些长链非编码RNA均可以影响脂肪干细胞的成肌分化。脂肪干细胞可通过直接分化为骨骼肌细胞或旁分泌各种细胞因子，调控炎症反应，抑制细胞凋亡，保护受损骨骼肌细胞，促进血管形成，招募内源性干细胞，促进骨骼肌功能和形态的修复。综合利用各种细胞因子和生长因子，结合三维支架，促进脂肪干细胞的增殖和成肌分化，构建组织工程肌肉是未来的研究方向。

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: 0000-0003-4642-5795(陈犹白)

关键词: 干细胞, 脂肪干细胞, 骨骼肌成肌细胞, 成肌分化, 影响因素

Abstract:

BACKGROUND: Skeletal muscle defect is a major concern of plastic and orthopedic surgeons due to poor regenerative capability of skeletal myocytes and limited clinical treatment. Recently, cell therapy and skeletal muscle engineering based on adipose-derived stem cells (ADSCs) open a new era for skeletal muscle injury repair, which attributes to merits of ADSCs including sufficiency, easy harvest, high yield, strong proliferation and paracrine capability, as well as differentiation potential towards skeletal myoblasts under specific induction.
OBJECTIVE: To summarize the process of ADSCs’ differentiation towards skeletal myoblasts, to analyze factors that may affect myogenic differentiation of ADSCs and their underlying mechanism, and to discuss the oncological safety of ADSC therapy and limits for clinical application.
METHODS: Search in PubMed using the following formula ((myogenic[Title]) OR myogenesis[Title]) AND adipose stem cell[MeSH Terms]) and in SinoMed using (((“adipose tissue”[Title]) AND “Stem cell”[Title]) AND “myo-”[Title]) was done on June 10th, 2017. References related to ADSCs’ myogenic differentiation or skeletal muscle repair were included, whereas repeated references were excluded.
RESULTS AND CONCLUSION: Forty-seven references in PubMed were selected. Within them, 26 were published in recent 5 years. Forty-seven references in SinoMed met the criteria; however 34 of them were about ADSCs’ differentiation towards myocardial cells and 6 were about ADSCs’ differentiation towards smooth muscle cells. Eventually, 50 references were included. ADSCs’ differentiation towards skeletal myoblasts under specific induction is a complicated process involving the interactions of varieties of genes, proteins and signal pathways. Besides the traditional in vitro chemical induction, conditioned medium or co-culture with myocytes can also facilitate ADSCs’ differentiation towards skeletal myoblasts. Chemicals, biomechanics, myogenic regulatory factors, cytokines, growth factors, microRNAs and lncRNA have effects on ADSCs myogenic differentiation. ADSCs can promote the repair of morphology and function of skeletal muscle through direct differentiation or indirect paracrine of cytokines, regulating inflammatory response, suppressing apoptosis, accelerating angiogenesis, and recruiting endogenous stem cells. The future study concerning skeletal muscle repair is expected to address the construction of tissue-engineered muscle by combining various cytokines and growth factors with three-dimensional scaffolds to promote ADSCs’ proliferation and differentiation. 

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, Adipose Tissue, Myoblasts, Skeletal, Tissue Engineering

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