Ge Tingting, Yu Qin, Liu Wei, Cong Li, Liu Lizhen, Wang Yan, Zhou Liping, Lin Deju
Department of Bioengineering, College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Department of Pediatrics, The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Mol Med Rep. 2016 Apr;13(4):3498-506. doi: 10.3892/mmr.2016.4945. Epub 2016 Feb 29.
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.
脯氨酰羟化酶抑制剂二甲基草酰甘氨酸(DMOG)在干细胞治疗方面受到越来越多的研究。先前的研究表明,内源性间充质干细胞(MSC)可通过药物预处理被动员到外周循环中。此外,我们之前的研究证实,DMOG作为一种新型动员剂,可诱导小鼠/大鼠MSC迁移到外周血液循环中。因此,本研究对腹腔注射DMOG后从小鼠收集的骨髓来源的MSC(BM-MSC)进行了特性研究。分别通过流式细胞术、分化诱导、细胞计数试剂盒-8、Transwell实验和酶联免疫吸附测定法,评估了从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。与NBM-MSC相比,DBM-MSC表现出相似的免疫表型和多向分化能力、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DMOG预处理小鼠的BM-MSC的生物学特性提供了新的见解。DBM-MSC与NBM-MSC表现出略有不同的特征;然而,它们可能对未来的干细胞治疗具有治疗潜力。此外,本研究表明,由于未观察到不良反应,DMOG可能在未来的临床试验中用作新型动员剂。