Department of Internal Medicine, Botucatu Medical School, São Paulo State University - UNESP, Botucatu, São Paulo, Brazil.
Institute of Biosciences, Department of Chemistry and Biochemistry, São Paulo State University - UNESP, Botucatu, São Paulo, Brazil.
PLoS One. 2018 Apr 11;13(4):e0194847. doi: 10.1371/journal.pone.0194847. eCollection 2018.
Human adipose tissue-derived stem cells (hASCs) have been subjected to extensive investigation because of their self-renewal properties and potential to restore damaged tissues. In the literature, there are several protocols for differentiating hASCs into osteoblasts, but there is no report on the control of cell viability during this process. In this study, we used osteoblasts derived from hASCs of patients undergoing abdominoplasty. The cells were observed at the beginning and end of bone matrix formation, and the expression of proteins involved in this process, including alkaline phosphatase and osteocalcin, was assessed. RANKL, Osterix, Runx2, Collagen3A1, Osteopontin and BSP expression levels were analyzed using real-time PCR, in addition to a quantitative assessment of protein levels of the markers CD45, CD105, STRO-1, and Nanog, using immunofluorescence. Rhodamine (Rho123), cytochrome-c, caspase-3, P-27, cyclin D1, and autophagy cell markers were analyzed by flow cytometry to demonstrate potential cellular activity and the absence of apoptotic and tumor cell processes before and after cell differentiation. The formation of bone matrix, along with calcium nodules, was observed after 16 days of osteoinduction. The gene expression levels of RANKL, Osterix, Runx2, Collagen3A1, Osteopontin, BSP and alkaline phosphatase activity were also elevated after 16 days of osteoinduction, whereas the level of osteocalcin was higher after 21 days of osteoinduction. Our data also showed that the cells had a high mitochondrial membrane potential and a low expression of apoptotic and tumor markers, both before and after differentiation. Cells were viable after the different phases of differentiation. This proposed methodology, using markers to evaluate cell viability, is therefore successful in assessing different phases of stem cell isolation and differentiation.
人脂肪组织来源的干细胞(hASCs)因其自我更新特性和修复受损组织的潜力而受到广泛研究。在文献中,有几种将 hASCs 分化为成骨细胞的方案,但没有关于在此过程中控制细胞活力的报告。在这项研究中,我们使用了来自接受腹部整形术患者的 hASCs 衍生的成骨细胞。在骨基质形成的开始和结束时观察细胞,并评估参与该过程的蛋白质的表达,包括碱性磷酸酶和骨钙素。使用实时 PCR 分析 RANKL、Osterix、Runx2、Collagen3A1、Osteopontin 和 BSP 的表达水平,此外还通过免疫荧光定量评估标记物 CD45、CD105、STRO-1 和 Nanog 的蛋白水平。使用 rhodamine(Rho123)、细胞色素-c、caspase-3、P-27、cyclin D1 和自噬细胞标记物通过流式细胞术分析,以证明潜在的细胞活性和细胞分化前后不存在凋亡和肿瘤细胞过程。在诱导成骨 16 天后观察到骨基质的形成,以及钙结节。在诱导成骨 16 天后,RANKL、Osterix、Runx2、Collagen3A1、Osteopontin、BSP 和碱性磷酸酶活性的基因表达水平也升高,而骨钙素的水平在诱导成骨 21 天后更高。我们的数据还表明,细胞在分化前后都具有高的线粒体膜电位和低表达的凋亡和肿瘤标志物。细胞在不同分化阶段后仍具有活力。因此,使用标记物评估细胞活力的这种方法成功地评估了干细胞分离和分化的不同阶段。