脂肪干细胞成脂分化的研究进展

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创伤或肿瘤导致的软组织缺损是整形科的常见问题,现有的组织瓣移植、人工材料充填或脂肪移植等方法均有一定局限性。脂肪干细胞(adipose-derived stem cells,ASCs)是来自脂肪组织的具有多向分化潜能的干细胞,基于ASCs的干细胞治疗,或利用其成脂分化能力构建组织工程脂肪,为软组织缺损的修复重建提供了新的思路,在整形美容和再生医学中展示了良好的前景。体外利用药物和化学试剂诱导ASCs成脂分化的方法已经非常成熟。支架材料通过模拟干细胞的体内微环境,可促进ASCs的黏附、增殖和成脂分化,其中脱细胞脂肪组织支架是目前脂肪组织工程支架材料的研究热点。研究显示ASCs的供体种属、性别、年龄、脂肪获取部位和方法等供体因素,细胞亚群、ASCs代数、培养液、冻存等实验因素,表皮细胞生长因子、成纤维细胞生长因子、血管内皮细胞生长因子、胰岛素样生长因子、骨形成蛋白、尼尔样1型分子等生长因子,胰岛素、糖皮质激素、雌激素、生长激素、瘦素、催产素和卡贝缩宫素等激素,异丁基甲基黄嘌呤、紫杉醇、胰高血糖素样肽等化学药物,放射线和激光等物理因素,以及Toll样受体、富血小板血浆和富血小板纤维蛋白、人腺病毒36亚型、核心结合因子α1等其他因素均可影响ASCs的成脂分化。因此综合利用各种上述因素,促进ASCs的增殖和定向分化,在整形美容和再生医学等领域具有重要的意义和应用前景。本文总结了诱导和验证ASCs成脂分化的方法,讨论了主要影响因素及其机制,介绍了解放军总医院整形修复科和美国MD安德森肿瘤中心整形科组织再生和分子细胞工程实验室(Tissue Regeneration and Molecular Cell Engineering Lab,TRAMCEL)的相关经验,展望了未来研究方向。“,”Soft tissue defect results from trauma and tumor resection is the common problem in plastic surgery. Existing methods such as tissue flap transplantation, artificial material filling and fat transplantation are not perfect. Adipose-derived stem cells (ASCs) are multipotent stem cells isolated from adipose tissue. Stem cell therapy and adipose tissue engineering based on the adipogenic differentiation capacity of ASCs are promising in plastic and aesthetic surgery and regenerative medicine. The in vitro induction of ASCs differentiation towards adipocyte using medication and chemical was well established. Previous studies showed that various scaffold including decellularized adipose tissue scaffold facilitated ASCs adhesion, proliferation and adipogenic differentiation through mimicking in vivo microenvironment, however its mechanism is not well understood. Factors which could affect ASCs adipocyte differentiation include donor factors such as species, age, gender, anatomic site, and harvesting technique; experimental factors such as cell subpopulation, cell passage, culture condition, and cryopreservation;growth factors such as epidermal growth factor, fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor, bone morphogenetic proteins, and Nel-like type 1 molecule; hormones such as insulin, glucocorticoids, estrogen, growth hormone, and leptin; chemical like IBMX, paclitaxel and glucagon-like peptide-1;physical factors like radiation and laser; other factors such as Toll-like receptors, platelet-rich plasma and fibrin, human adenovirus-36,and core binding factorα1. Therefore, it is crucial to combine the abovementioned factors and scaffold for improvement of ASCs proliferation and specific differentiation. This review focused on the induction and verification methods, factors and their mechanisms of ASCs adipogenic differentiation. We also introduced our experience and looked forward the future research interest of ASCs adipogenic differentiation based on current issues.
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