Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
Tissue Eng Part A. 2010 Jul;16(7):2161-82. doi: 10.1089/ten.TEA.2009.0629.
Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-gamma treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.
成体干细胞,如人间质干细胞(hMSCs),表现出有限的增殖能力,并且在长期培养后,丧失其分化能力,因此不是组织工程的最佳细胞来源。人胚胎干细胞(hESCs)是该领域的一个重要新资源,但一个主要缺点是受体中形成肿瘤的风险。一种替代方法是使用源自 hESCs 的祖细胞,这些祖细胞的谱系限制更多,但不会形成畸胎瘤。我们最近从 hESCs 中衍生出一种细胞系,称为 hESC 衍生中胚层祖细胞(hES-MPs),在这里,我们使用全基因组微阵列分析报告说,hES-MPs 的衍生过程导致 hESC 特征基因的表达显著改变,达到与 hMSCs 高度相似的表达水平。然而,hES-MPs 表现出更高的增殖能力和更长的端粒。hES-MPs 在干扰素-γ处理前后 HLA Ⅱ类蛋白的表达也较低,表明这些细胞可能具有一定的免疫特权,并可潜在用于 HLA 不相容的移植。因此,hES-MPs 是组织工程应用和基于干细胞的中胚层组织治疗中 hMSCs 的一种有吸引力的替代物。