Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences and Pathology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Animal Sciences, School of Life Sciences, University of Kharazmi, Tehran, Iran.
Biofactors. 2014 Nov-Dec;40(6):624-35. doi: 10.1002/biof.1192. Epub 2014 Nov 19.
Human umbilical cord-derived mesenchymal stem cells (HUCMSCs) are multipotent fetal stem cells that differentiate into various cell lineages. In recent years, they have gained attention for therapeutic applications but very little is known about their sensitivity to chemical agents such as widely used retinoic acid (RA). As a morphogen inducing differentiation of mesenchymal stem cells, RA has for a long time been known to be a potent teratogen promoting craniofacial and limb abnormality in vertebrate embryos. Here, using MTT assay and EB/AO staining as well as TUNEL assay we show that RA in a concentration-dependent manner induces apoptosis through upregulating Caspase expression and increasing Bax/Bcl2 ratio. Moreover, different biological parameters such as initial time seeding, cell density, passage number and duration of RA treatment play a major role in HUCMSCs cytotoxic response to this agent.
人脐带间充质干细胞(HUCMSCs)是多能性胎儿干细胞,可分化为多种细胞谱系。近年来,它们因治疗应用而受到关注,但对其对化学试剂(如广泛使用的维甲酸(RA))的敏感性知之甚少。作为诱导间充质干细胞分化的形态发生素,RA 长期以来一直被认为是一种有效的致畸剂,可促进脊椎动物胚胎的颅面和肢体异常。在这里,我们通过 MTT 检测和 EB/AO 染色以及 TUNEL 检测表明,RA 通过上调 Caspase 表达和增加 Bax/Bcl2 比值,以浓度依赖的方式诱导细胞凋亡。此外,初始接种时间、细胞密度、传代数和 RA 处理持续时间等不同的生物学参数在 HUCMSCs 对该药物的细胞毒性反应中起着重要作用。