Li Miaomiao, Yang Junqing, Cheng Oumei, Peng Zhe, Luo Yin, Ran Dongzhi, Yang Yang, Xiang Pu, Huang Haifeng, Tan Xiaodan, Wang Hong
College of Pharmacy, Chongqing Medical University, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, China.
College of Pharmacy, Chongqing Medical University, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
Ther Adv Chronic Dis. 2021 Mar 19;12:2040622321998139. doi: 10.1177/2040622321998139. eCollection 2021.
Human bone marrow mesenchymal stem cells (hBMSCs) could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinson's disease (PD) models. Liver X receptors (LXRs) are involved in the maintenance of the normal function of central nervous system myelin. Therefore, the previous work of our team has found the induction of cocktail-induced to dopaminergic (DA) phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), and TO901317 (an agonist of LXRs) with 87.42% of efficiency in a 6-day induction period. But we did not verify whether the induced cells had the corresponding neural function.
Expressions of LXRα, LXRβ, and tyrosine hydroxylase (TH) were detected by immunofluorescence and western blot. Adenosine triphosphate-binding cassette transporter A1 (ABCA1) was detected by quantitative real-time PCR. The induced cells were transplanted into PD rats to study whether the induced cells are working.
The induced cells can release the dopamine transmitter; the maximum induction efficiency of differentiation of hBMSCs into DA neurons was 91.67% under conditions of combined use with TO901317 and growth factors (GF). When the induced-cells were transplanted into PD rats, the expression of TH in the striatum increased significantly, and the behavior of PD rats induced by apomorphine was significantly improved.
The induced cells have the function of DA neurons and have the potential to treat PD. TO901317 promoted differentiation of hBMSCs into DA neurons, which may be related to activation of the LXR-ABCA1 signaling pathway.
人骨髓间充质干细胞（hBMSCs）可分化为产生多巴胺的细胞，并改善帕金森病（PD）模型中的行为缺陷。肝脏X受体（LXRs）参与中枢神经系统髓鞘正常功能的维持。因此，我们团队之前的工作发现，使用音猬因子（SHH）、成纤维细胞生长因子8（FGF8）、碱性成纤维细胞生长因子（bFGF）和TO901317（一种LXRs激动剂）可在6天的诱导期内将成年大鼠BMSCs诱导为多巴胺能（DA）表型，诱导效率为87.42%。但我们并未验证诱导细胞是否具有相应的神经功能。
通过免疫荧光和蛋白质印迹法检测LXRα、LXRβ和酪氨酸羟化酶（TH）的表达。通过定量实时PCR检测三磷酸腺苷结合盒转运体A1（ABCA1）。将诱导细胞移植到PD大鼠体内，研究诱导细胞是否起作用。
诱导细胞可释放多巴胺递质；在与TO901317和生长因子（GF）联合使用的条件下，hBMSCs向DA神经元分化的最大诱导效率为91.67%。当将诱导细胞移植到PD大鼠体内时，纹状体中TH的表达显著增加，阿扑吗啡诱导的PD大鼠行为得到显著改善。
诱导细胞具有DA神经元的功能，具有治疗PD的潜力。TO901317促进hBMSCs向DA神经元分化，这可能与LXR-ABCA1信号通路的激活有关。
