In vitro and in vivo properties of distinct populations of amniotic fluid mesenchymal progenitor cells.

In vitro and in vivo properties of distinct populations of amniotic fluid mesenchymal progenitor cells.
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DOI:
10.1111/j.1582-4934.2010.01180.x
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发表时间:
2011-09
影响因子:
5.3
通讯作者:
Anagnou NP
Anagnou NP
中科院分区:
医学2区
文献类型:
--
作者:
Roubelakis MG;Bitsika V;Zagoura D;Trohatou O;Pappa KI;Makridakis M;Antsaklis A;Vlahou A;Anagnou NP

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人骨髓间充质祖细胞(MPC)在组织修复和再生医学中具有广阔的应用前景。MPC代表多能的贴壁细胞,能够分化为多种间充质细胞,如成骨细胞、脂肪细胞或软骨细胞。最近,我们发现并表征了人类中期羊水(AF)是一种新的MPC来源。在此,我们发现AF-MPC的早期集落由两种形态不同的贴壁细胞组成,称为纺锤形(SS)和圆形(RS)。对这两个群体的详细分析表明,SS-AF-MPC高水平表达CD90抗原,并显示出更大的增殖和分化潜力。为了更好地表征这两个群体的分子同一性,我们创建了SS-AF-MPC和RS-AF-MPC的比较蛋白质组图谱,鉴定了25个差异表达的蛋白质和10个在RS-AF-MPC中唯一表达的蛋白质。此外,SS-AF-MPC在体外对纤维连接蛋白和层粘连蛋白等细胞外基质的迁移能力明显高于RS-AF-MPC,因此我们进一步评价了SS-AF-MPC作为体内治疗工具的可能性。因此,我们检测了GFP-慢病毒转导的SS-AF-MPC是否保持了其干细胞的特性、增殖和分化潜能。将GFP-SS-AF-MPC成功地导入免疫抑制小鼠体内,分布于不同组织,并在体内长期存活。综上所述,这些结果表明,AF-MPC至少由两个不同的MPC群体组成。此外,根据集落形态和CD90表达分离的SS-AF-MPC代表了唯一可以在培养中容易扩增的MPC群体,并作为未来体内治疗应用的有效工具。
Human mesenchymal progenitor cells (MPCs) are considered to be of great promise for use in tissue repair and regenerative medicine. MPCs represent multipotent adherent cells, able to give rise to multiple mesenchymal lineages such as osteoblasts, adipocytes or chondrocytes. Recently, we identified and characterized human second trimester amniotic fluid (AF) as a novel source of MPCs. Herein, we found that early colonies of AF-MPCs consisted of two morphologically distinct adherent cell types, termed as spindle-shaped (SS) and round-shaped (RS). A detailed analysis of these two populations showed that SS-AF-MPCs expressed CD90 antigen in a higher level and exhibited a greater proliferation and differentiation potential. To characterize better the molecular identity of these two populations, we have generated a comparative proteomic map of SS-AF-MPCs and RS-AF-MPCs, identifying 25 differentially expressed proteins and 10 proteins uniquely expressed in RS-AF-MPCs. Furthermore, SS-AF-MPCs exhibited significantly higher migration ability on extracellular matrices, such as fibronectin and laminin in vitro, compared to RS-AF-MPCs and thus we further evaluated SS-AF-MPCs for potential use as therapeutic tools in vivo. Therefore, we tested whether GFP-lentiviral transduced SS-AF-MPCs retained their stem cell identity, proliferation and differentiation potential. GFP-SS-AF-MPCs were then successfully delivered into immunosuppressed mice, distributed in different tissues and survived longterm in vivo. In summary, these results demonstrated that AF-MPCs consisted of at least two different MPC populations. In addition, SS-AF-MPCs, isolated based on their colony morphology and CD90 expression, represented the only MPC population that can be expanded easily in culture and used as an efficient tool for future in vivo therapeutic applications.
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