目的 基于转录组数据探讨脂肪组织（AD）、胎盘绒毛膜（HC）、胎盘羊膜（HA）和脐带（UC）来源的间充质干细胞 （MSCs） 的生物学异质性。方法 从人 AD、HC、HA 和 UC 中分离 MSCs，流式细胞术检测细胞表面阳性标志物（CD73、CD90、CD105）和阴性标志物（CD14、CD34、CD45、CD79a、HLA-DR）的表达，改良版茜素红染色、油红O 染色、阿利辛蓝染色检测细胞的三系分化能力；Trizol 法提取细胞总 RNA，用于转录组测序，应用 GFOLD（1.1.4）进行差异基因表达分析；使用 DAVID 数据库对差异表达的基因进行基因本体（GO）功能富集分析。结果 P2 代的不同来源的 MSCs，CD73、CD90、CD105 均为阳性表达，CD14、CD34、CD45、CD79a、HLA-DR 均为阴性表达，培养的 MSCs 均具有三系分化能力。新生儿来源的 MSCs（HA、HC 和 UC）相关性大于成人来源的 MSCs（AD），在功能富集分析中，与来源于 AD 的MSCs 相比，HA 和 UC 来源的 MSCs 表现出更优异的增殖能力。来源于 AD 的 MSCs 有更好的分化潜力以及促进血管生成能力，而来源于 UC 的 MSCs 支持神经元的发育并分泌可以调节免疫环境的趋化因子和抗炎因子。结论 不同来源的 MSCs 具有不同的生物学特征，提示不同来源的 MSCs 可能具有不同临床应用的最佳选择。

Objective To investigate the biological heterogeneity of adipose tissue (AD), placental chorionic membrane (HC), placental amniotic membrane (HA) and umbilical cord (UC) derived mesenchymal stem cells (MSCs) based on transcriptome data. Methods MSCs were isolated from human AD, HC, HA and UC, and the expressions of positive markers (CD73, CD90, CD105) and negative markers (CD14, CD34, CD45, CD79a, HLA-DR) on the cell surface were detected by flow cytometry. Improved alizarin red staining, oil red O staining and alisin blue staining were used to detect the three-line differentiation ability of the cells. Total RNA was extracted by Trizol method for transcriptome sequencing, and differential gene expression was analyzed by GFOLD (1.1.4). The gene ontology (GO) functional enrichment analysis of differentially expressed genes was performed using the DAVID database. Results In P2 generation of MSCs from different sources, CD73, CD90 and CD105 were all positively expressed, while CD14, CD34, CD45, CD79a and HLA-DR were all negatively expressed. The cultured MSCs all had the ability of three-line differentiation. Correlation analysis revealed that MSCs derived from neonatal sources (HA, HC, and UC) were more closely related to each other than those derived from adult sources (AD). In functional enrichment analysis, compared to MSCs from AD, those derived from HA and UC showed superior proliferative abilities. AD-derived MSCs demonstrated better differentiation potential and angiogenesis ability. In contrast, UC-derived MSCs supported neuronal development and secreted chemokines and antiinflammatory factors that regulate the immune environment. Conclusion MSCs derived from different sources possess distinct biological characteristics, suggesting that the optimal choice for clinical applications may vary depending on the source of MSCs.

R965

国家重点研发计划干细胞及相关治疗产品质量控制和非临床评价关键技术与规范研究项目（2021YFA1101603）；天津市科技计划项目细胞产品开发和临床应用的研究（22ZYJDSY00150）；天津市科技计划项目细胞制品的成药性及转化研究（23ZGCX‐QY00050）