脂肪干细胞表型和标记物的研究进展

A review on phenotype and markers of adipose-derived stem cells

由于脂肪供体、提取方法、分离、培养、体内外微环境、鉴定时的细胞代数和检测方法等诸多因素的差异,迄今为止尚未发现脂肪干细胞(adipose-derived stem cell,ASCs)的特异性标记物。本文总结了所有ASCs的相关标记物,发现阳性标记物集中在基质细胞、间充质干细胞和成纤维细胞标记物上,而阴性标记物主要是造血系细胞标记物,ASCs的争议标记物主要以骨髓间充质干细胞(bone marrow stem cells,BMSCs)、血管内皮细胞和周细胞标记物为主,这也体现了关于ASCs体内来源的争议。体内、刚分离的和体外培养初期的ASCs表达CD34,但经长时间体外培养后,其表达逐渐降低最后完全消失。这证实了ASCs体内外的表型差异,因此不能通过检测体外长期培养后的ASCs来确定体内的ASCs表型。Stro-1等干性标记物在ASCs的表达对鉴别ASCs有重要意义,但能否作为ASCs的常规标记物用于鉴定ASCs,尚需要进一步的研究。基质血管成分(Stromal vascular fraction,SVF)和ASCs不同亚群的表型差异提示了ASCs的体内起源,即BMSCs、周细胞或成纤维细胞,但尚无定论。ASCs表达CD36、CD49d,不表达CD48f、CD104,BMSCs则相反,这是鉴别ASCs和BMSCs的表型依据。本文还介绍了美国德克萨斯大学MD安德森肿瘤中心整形科组织再生与分子细胞工程实验室(Tissue Regeneration and Molecular Cell Engineering Lab,TRAMCEL)在ASCs表型方面的研究经验,探讨了ASCs表型研究目前存在的问题和未来的发展方向。

No consensus has been made so far on the specific markers of adipose-derived stem cells（ASCs） due to the differences of fat donor,micro-environment between in vivo and in vitro,cell passages and lack of standard of harvest,isolation,culture,et al.We reviewed all markers of ASCs and found that most positive markers are stromal cells and mesenchymal stem cells markers, while most negative markers were hematopoietic cells markers.The controversial markers of ASCs were basically bone marrow stem cells（BMSCs）,vascular endothelial cells and pericytes markers. In vivo, fresh-isolated ASCs and ASCs from initial passages of in vitro expansion were CD34＋, however the expression of CD34 was decreasing with long-term expansion in vitro and finally vanish. This was the reason of controversy on CD34 expression from literatures and the evidence that ASCs have different phenotypes in vivo and in vitro.Furthermore,stemness markers like Stro-1 were important and promising in identifying ASCs, however further studies are needed to determine their role in ASCs identification. According to the phenotypic differences between Stromal vascular fraction（SVF） cells and ASCs subpopulations,we speculated that ASCs in vivo may origin from BMSCs,pericytes or fibroblasts. We compared the phenotypes of ASCs with BMSCs and found that ASCs are CD36＋/CD49d＋/ CD48f-/CD104-, while BMSCs were the opposite,which could be used to identify ASCs from BMSCs.Finally,we introduced the experience of Tissue Regeneration and Molecular Cell Engineering Lab, Department of Plastic Surgery, MD Anderson Cancer Center and predicted the future research interests of ASCs phenotypes and markers based on our experience and current issues.