Harkness Linda, Twine Natalie A, Abu Dawud Raed, Jafari Abbas, Aldahmash Abdullah, Wilkins Marc R, Adjaye James, Kassem Moustapha
Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark; NSW Systems Biology Initiative, University of New South Wales, Sydney, NSW, Australia.
Bone Rep. 2015 Aug 4;3:32-39. doi: 10.1016/j.bonr.2015.07.002. eCollection 2015 Dec.
Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal) that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited ≥ 2-fold change (FC) in hESC-stromal and BM-hMSC, respectively with 172 genes common to both cell types. Functional annotation of significantly changing genes revealed similarities in gene ontology between the two cell types. Interestingly, genes in categories of cell adhesion/motility and epithelial-mesenchymal transition (EMT) were highly enriched in hESC-stromal whereas genes associated with cell cycle processes were enriched in hMSC-TERT. This data suggests that while hESC-stromal cells exhibit a similar molecular phenotype to hMSC-TERT, differences exist that can be explained by ontological differences between these two cell types. hESC-stromal cells can thus be considered as a possible alternative candidate cells for hMSC, to be employed in regenerative medicine protocols.
人骨髓来源的基质（骨骼）干细胞（BM-hMSC）正被越来越多地用于组织再生的临床试验中。其临床应用的一个限制因素是无法获得足够数量的细胞。人胚胎干细胞（hESC）可为治疗提供无限的临床级细胞来源。我们已从hESC中生成了类似MSC的细胞（此处称为hESC-基质细胞），这些细胞表现出表面标志物，并能分化为成骨细胞和脂肪细胞，类似于BM-hMSC。在本研究中，我们使用微阵列分析来比较hESC-基质细胞和永生化BM-hMSC细胞（hMSC-TERT）的分子表型。在表达水平高于基线的7379个基因中，未分化的hESC-基质细胞和BM-hMSC之间只有9.3%的基因存在差异表达。体外成骨细胞诱导后，hESC-基质细胞和BM-hMSC中分别有665个和695个基因表现出≥2倍变化（FC），两种细胞类型共有172个基因。对显著变化基因的功能注释揭示了两种细胞类型在基因本体论上的相似性。有趣的是，细胞黏附/运动和上皮-间质转化（EMT）类别的基因在hESC-基质细胞中高度富集，而与细胞周期进程相关的基因在hMSC-TERT中富集。这些数据表明，虽然hESC-基质细胞表现出与hMSC-TERT相似的分子表型，但存在的差异可以通过这两种细胞类型在本体论上的差异来解释。因此，hESC-基质细胞可被视为hMSC的一种可能替代候选细胞，用于再生医学方案。
