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Characterization of bone marrow-derived mesenchymal stem cells from dimethyloxallyl glycine-preconditioned mice: Evaluation of the feasibility of dimethyloxallyl glycine as a mobilization agent

机译:表征二甲基草酸甘氨酸预处理小鼠的骨髓间充质干细胞:评估二甲基草酸甘氨酸作为动员剂的可行性

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摘要

The prolyl hydroxylase inhibitor dimethyloxallyl glycine (DMOG) has been increasingly studied with regards to stem cell therapy. Previous studies have demonstrated that endogenous mesenchymal stem cells (MSCs) may be mobilized into peripheral circulation by pharmaceutical preconditioning. In addition, our previous study confirmed that DMOG, as a novel mobilization agent, could induce mouse/rat MSC migration into peripheral blood circulation. Therefore, the present study conducted studies to characterize bone marrow-derived MSCs (BM-MSCs) collected from mice following DMOG intraperitoneal injection. The surface antigen immune phenotype, differentiation capability, proliferative ability, migratory capacity and paracrine capacity of the BM-MSCs collected from DMOG-preconditioned mice (DBM-MSCs) or normal saline-treated mice (NBM-MSCs) were evaluated by means of flow cytometry, differentiation induction, Cell Counting kit-8, Transwell assay and enzyme-linked immunosorbent assay, respectively. Compared with NBM-MSCs, DBM-MSCs displayed a similar immune phenotype and multilineage differentiation capability, reduced proliferative ability and migratory capacity, and similar transforming growth factor and platelet-derived growth factor secretion capacity. These results provide a novel insight into the biological properties of BM-MSCs from mice preconditioned with DMOG. DBM-MSCs exhibited slightly distinct characteristics to NBM-MSCs; however, they may have therapeutic potential for future stem cell therapy. In addition, the present study suggested that DMOG may be used as a novel mobilization agent in future clinical trials as no adverse effects were observed.
机译:脯氨酰羟化酶抑制剂二甲基草烯丙基甘氨酸(DMOG)已在干细胞治疗方面得到越来越多的研究。先前的研究表明,内源性间充质干细胞(MSCs)可通过药物预处理动员到外周循环中。此外,我们先前的研究证实DMOG作为一种新型动员剂,可以诱导小鼠/大鼠MSC迁移到外周血循环中。因此,本研究进行了研究,以表征DMOG腹腔注射后从小鼠收集的骨髓来源的MSC(BM-MSC)。通过流动评估从DMOG预处理小鼠(DBM-MSC)或生理盐水处理小鼠(NBM-MSC)收集的BM-MSC的表面抗原免疫表型,分化能力,增殖能力,迁移能力和旁分泌能力细胞计数,分化诱导,Cell Counting kit-8,Transwell测定和酶联免疫吸附测定。与NBM-MSCs相比,DBM-MSCs具有相似的免疫表型和多谱系分化能力,降低的增殖能力和迁移能力,以及相似的转化生长因子和血小板衍生生长因子分泌能力。这些结果为使用DMOG预处理的小鼠的BM-MSC的生物学特性提供了新颖的见解。 DBM-MSC具有与NBM-MSC略有不同的特征。然而,它们可能具有未来干细胞治疗的治疗潜力。此外,本研究表明,由于未观察到不良反应,DMOG可在未来的临床试验中用作新型动员剂。

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