Tai Chenxu, Wang Liudi, Xie Yuanyuan, Gao Tianyun, Huang Feifei, Wang Bin
Clinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Cells Tissues Organs. 2021;210(1):45-57. doi: 10.1159/000513038. Epub 2021 Mar 29.
For potential clinical applications in the future, we investigated the distinct biological features of mesenchymal stromal cells (MSCs) derived from different origin areas of human placenta and individual heterogeneity among different donors. Chorionic plate MSCs (CP-MSCs), amniotic membrane MSCs (AM-MSCs), and decidual plate MSCs (DP-MSCs) were isolated from 5 human placentae and were analyzed in terms of main features of MSCs including surface marker profile, growth, differentiation potential, immune regulation capability, and tubulin acetylation (Ac-tubulin). The expression profile of surface markers in the 3 types of MSCs derived from the 5 donors was relatively stable. Heterogeneity was found in growth, differentiation potential, and immune regulation among MSCs according to the different areas of isolation and different donors. CP-MSCs and AM-MSCs derived from the placentae of donors 1-3 had a higher osteogenic differentiation potential than the corresponding DP-MSCs, but those derived from the placentae of donors 4 and 5 had a markedly lower osteogenic differentiation potential than DP-MSCs. All CP-MSCs derived from donors 1-3 had the highest adipogenic differentiation potential, but CP-MSCs derived from donors 4 and 5 did not show strong capability of adipogenic differentiation. CP-MSCs markedly inhibited the proliferation of peripheral blood mononuclear cells (PBMCs) induced by phytohemagglutinin, whereas AM- and DP-MSCs did not. All MSCs decreased the proportion of CD3+/CD8-/IFN-γ+ Th1 and CD3+/CD8-/IL17+ Th17 cells, but increased the proportion of Treg cells in PBMCs, with individual differences among the 5 donors. DP-MSCs from donors 1 and 2 had higher levels of Ac-tubulin compared with CP- and AM-MSCs. However, the levels of Ac-tubulin in AM-MSCs from donors 3 and 5 were higher than those of the other 2 types of MSCs. Our results revealed that there was tissue-specific heterogeneity among the 3 types of MSCs from different origin tissues of placenta and individual heterogeneity among donors. In future, the pre-selected placenta-derived MSCs with specific biological advantages may improve the curative effect of cell therapy in different situations.
为了探索未来潜在的临床应用，我们研究了源自人胎盘不同区域的间充质基质细胞（MSCs）的独特生物学特性以及不同供体之间的个体异质性。从5份人胎盘中分离出绒毛膜板间充质基质细胞（CP-MSCs）、羊膜间充质基质细胞（AM-MSCs）和蜕膜板间充质基质细胞（DP-MSCs），并从MSCs的主要特性方面进行分析，包括表面标志物谱、生长、分化潜能、免疫调节能力和微管蛋白乙酰化（Ac-微管蛋白）。来自5个供体的3种MSCs表面标志物的表达谱相对稳定。根据分离区域和供体不同，MSCs在生长、分化潜能和免疫调节方面存在异质性。来自供体1-3胎盘的CP-MSCs和AM-MSCs比相应的DP-MSCs具有更高的成骨分化潜能，但来自供体4和5胎盘的CP-MSCs和成骨分化潜能明显低于DP-MSCs。所有来自供体1-3的CP-MSCs具有最高的成脂分化潜能，但来自供体4和5的CP-MSCs没有显示出强大的成脂分化能力。CP-MSCs显著抑制植物血凝素诱导的外周血单个核细胞（PBMCs）增殖，而AM-MSCs和DP-MSCs则无此作用。所有MSCs均降低了PBMCs中CD3+/CD8-/IFN-γ+ Th1和CD3+/CD8-/IL17+ Th17细胞的比例，但增加了Treg细胞的比例，5个供体之间存在个体差异。与CP-MSCs和AM-MSCs相比，来自供体1和2的DP-MSCs具有更高水平的Ac-微管蛋白。然而来自供体3和5的AM-MSCs中Ac-微管蛋白水平高于其他2种MSCs类型。我们结果显示胎盘不同来源组织的3种MSCs之间存在组织特异性异质性，且供体之间存在个体异质性差异。未来，预先选择具有特定生物学优势胎盘来源MSCs可能会改善不同情况下细胞治疗疗效。
