Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Unit 951, 7435 Fannin Street, Houston, TX 77054, USA.
Biol Cell. 2011 Apr;103(4):197-208. doi: 10.1042/BC20100117.
Although MSCs (mesenchymal stem cells) and fibroblasts have been well studied, differences between these two cell types are not fully understood. We therefore comparatively analysed antigen and gene profiles, colony-forming ability and differentiation potential of four human cell types in vitro: commercially available skin-derived fibroblasts [hSDFs (human skin-derived fibroblasts)], adipose tissue-derived stem cells [hASCs (human adipose tissue-derived stem cells)], embryonic lung fibroblasts (WI38) and dermal microvascular endothelial cells [hECs (human dermal microvascular endothelial cells)].
hSDFs, hASCs and WI38 exhibited a similar spindle-like morphology and expressed same antigen profiles: positive for MSC markers (CD44, CD73 and CD105) and fibroblastic markers [collagen I, HSP47 (heat shock protein 47), vimentin, FSP (fibroblast surface protein) and αSMA (α smooth muscle actin)], and negative for endothelial cell marker CD31 and haemopoietic lineage markers (CD14 and CD45). We further analysed 90 stem cell-associated gene expressions by performing real-time PCR and found a more similar gene expression pattern between hASCs and hSDFs than between hSDFs and WI38. The expression of embryonic stem cell markers [OCT4, KLF4, NANOG, LIN28, FGF4 (fibroblast growth factor 4) and REST] in hASCs and hSDFs was observed to differ more than 2.5-fold as compared with WI38. In addition, hSDFs and hASCs were able to form colonies and differentiate into adipocytes, osteoblasts and chondrocytes in vitro, but not WI38. Moreover, single cell-derived hSDFs and hASCs obtained by clonal expansion were able to differentiate into adipocytes and osteoblasts. However, CD31 positive hECs did not show differentiation potential.
These findings suggest that (i) so-called commercially available fibroblast preparations from skin (hSDFs) consist of a significant number of cells with differentiation potential apart from terminally differentiated fibroblasts; (ii) colony-forming capacity and differentiation potential are specific important properties that discriminate MSCs from fibroblasts (WI38), while conventional stem cell properties such as plastic adherence and the expression of CD44, CD90 and CD105 are unspecific for stem cells.
尽管间充质干细胞（MSCs）和成纤维细胞已经得到了很好的研究，但这两种细胞类型之间的差异尚未完全了解。因此，我们在体外比较分析了四种人源细胞类型的抗原和基因谱、集落形成能力和分化潜能：市售皮肤来源成纤维细胞[hSDFs（人皮肤来源成纤维细胞）]、脂肪组织来源的干细胞[hASCs（人脂肪组织来源的干细胞）]、胚胎肺成纤维细胞（WI38）和真皮微血管内皮细胞[hECs（人真皮微血管内皮细胞）]。
hSDFs、hASCs 和 WI38 表现出相似的纺锤形形态，并表达相同的抗原谱：MSC 标志物（CD44、CD73 和 CD105）和成纤维细胞标志物[胶原 I、HSP47（热休克蛋白 47）、波形蛋白、FSP（成纤维细胞表面蛋白）和αSMA（α平滑肌肌动蛋白）]阳性，内皮细胞标志物 CD31 和造血谱系标志物[CD14 和 CD45]阴性。我们通过实时 PCR 进一步分析了 90 种与干细胞相关的基因表达，发现 hASCs 和 hSDFs 之间的基因表达模式比 hSDFs 和 WI38 之间更相似。hASCs 和 hSDFs 中胚胎干细胞标志物[OCT4、KLF4、NANOG、LIN28、FGF4（成纤维细胞生长因子 4）和 REST]的表达差异超过 2.5 倍，而 WI38 则没有。此外，hSDFs 和 hASCs 能够在体外形成集落并分化为脂肪细胞、成骨细胞和软骨细胞，但 WI38 则不能。此外，通过克隆扩增获得的单个细胞衍生的 hSDFs 和 hASCs 能够分化为脂肪细胞和成骨细胞。然而，CD31 阳性的 hECs 没有表现出分化潜能。
这些发现表明：（i）所谓的市售皮肤成纤维细胞制剂（hSDFs）除了终末分化的成纤维细胞外，还包含大量具有分化潜能的细胞；（ii）集落形成能力和分化潜能是区分 MSC 和成纤维细胞（WI38）的重要特性，而传统的干细胞特性，如贴壁和 CD44、CD90 和 CD105 的表达，对干细胞来说并不特异。
