Effects of Donor Age, Gender, and In Vitro Cellular Aging on the Phenotypic, Functional, and Molecular Characteristics of Mouse Bone Marrow-Derived Mesenchymal Stem Cells
Effects of Donor Age, Gender, and In Vitro Cellular Aging on the Phenotypic, Functional, and Molecular Characteristics of Mouse Bone Marrow-Derived Mesenchymal Stem Cells
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DOI：
10.1089/scd.2010.0280
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发表时间：
2011-09-01
影响因子：
4
通讯作者：
Perez, Sonia A.
中科院分区：
文献类型：
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作者：
Katsara, Olga;Mahaira, Louisa G.;Perez, Sonia A.
间充质干细胞（Mesenchymal stem cells，MSCs）是一种重要的成体干细胞，在再生医学领域具有广泛的应用前景。考虑到小鼠模型在动物模型中的重要性，对源自BALB/c物种的骨髓MSC（BM-MSC）群体进行彻底表征是必要的。在本研究中，我们研究了性别、年龄和体外培养对BM-MSCs基本特性（增殖、分化和免疫抑制潜力）的影响。我们发现成年小鼠骨髓中的祖细胞频率下降，所有雌性供体中的MSC频率降低，体外增殖后BM-MSC增殖率增加。我们还检测了BM-MSCs的3种主要胚胎干细胞转录因子Oct 3/4、Sox-2和Nanog的表达，以及2种mRNA结合蛋白，编码区决定簇结合蛋白/胰岛素样生长因子2 mRNA结合蛋白1的表达。（Crd-bp/Imp 1）和无精子症样蛋白（Dazl），它们在原始干细胞中表达，脐带血造血干细胞和羊水干细胞。此外，据报道，这两个基因对胚胎发育至关重要。因此，在这项研究中，我们报告，为第一次，Crd-bp/Imp 1和Dazl在BM-MSCs中的表达。Dazl、Oct 3/4和Sox 2的检测水平相对较低，而Crd-bp/Imp 1、其主要靶点c-Myc以及Nanog的表达水平相对较低，与性别、供体年龄或体外传代无关。这些发现可以进一步支持MSC群体老化的外在理论和胚胎基因在成体干细胞生理学中的潜在意义。
Mesenchymal stem cells (MSCs) are a very important adult stem cell population with a multitude of potential applications in regenerative medicine. The thorough characterization of the bone marrow MSC (BM-MSC) population derived from the BALB/c species was essential, considering the significance of the murine model amongst animal models. In the present study, we examined the effect of gender, age, and in vitro culture on the basic properties (proliferation, differentiation, and immunosuppressive potential) of BM-MSCs. We found a decline in the progenitor frequencies from the BM of adult mice, lower MSC frequencies in all female donors, and an increase in the BM-MSC proliferation rate upon in vitro propagation. We also examined BM-MSCs for the expression of the 3 major embryonic stem cell transcription factors, Oct3/4, Sox-2, and Nanog, as well as 2 mRNA binding proteins, coding region determinant binding protein/insulin-like growth factor 2 mRNA binding protein 1 (Crd-bp/Imp1) and Deleted in azoospermia-like (Dazl), which are expressed in primitive stem cells, umbilical cord blood-hematopoietic stem cells and amniotic fluid stem cells, respectively. Further, it has been reported that these 2 genes are critical for embryonic development. In this study, therefore, we report, for the first time, the expression of Crd-bp/Imp1 and Dazl in BM-MSCs. Dazl, Oct3/4, and Sox2 were detected in relatively low levels in contrast to Crd-bp/Imp1, its major target c-Myc, as well as Nanog, which were expressed redundantly, irrespective of sex, donor age, or in vitro passaging. These findings could further support the extrinsic theory of aging of the MSC population and the potential implication of embryonic genes in adult stem cell physiology.