scholarly journals Effect of TO901317 on GF to promote the differentiation of human bone marrow mesenchymal stem cells into dopamine neurons on Parkinson’s disease

2021 ◽  
Vol 12 ◽  
pp. 204062232199813
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

2016 ◽  
Vol 117 (9) ◽  
pp. 2128-2137 ◽  
Author(s):  
Stefanos Kalomoiris ◽  
Andrew C. Cicchetto ◽  
Kinga Lakatos ◽  
Jan A. Nolta ◽  
Fernando A. Fierro

2020 ◽  
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  

Abstract Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinson's disease (PD) models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptors (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. The previous work of our team have reported the induction of cocktail-induced da phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF) and TO901317 (agonist of LXRs) with 87.42% of efficiency in 6 days of period of induction. But it did not verify whether the induced cells had the corresponding neural function. Methods: The present study was to investigate the effect of TO901317 on the differentiation of hBMSCs into dopaminergic (DA) neurons. In vitro, the cells were divided into control group, GF group and LXR+GF group. Neuronal markers (Tuj1, Neun and Nestin) and DA neuron markers (tyrosine hydroxylase, TH) were detected to explore the optimal concentration, optimal addition time and optimal induction time of TO901317 to promote hBMSCs differentiation. Determine induced cells’ DA neuron properties by detecting dopamine release. To clarify its underlying mechanisms, the expressions of LXRa, LXRb and ABCA1 were detected. In vivo, male Sprague Dawley (SD) rats were divided into control group, 6-OHDA group (model group) and 6-OHDA+Cells group (cell transplantation group) to observe whether cell transplantation had a therapeutic effect on PD. Results: TO901317 significantly enhanced the differentiation of hBMSCs into DA neurons. Compared to control group and GF group, only the LXR+GF group released dopamine by the result of enzyme linked immunosorbent assay (ELISA). Compared with the control group and GF group, the optimal time for differentiation of hBMSCs treated by 0.5mM TO901317 combined with GF was six days in LXR+GF group. And the maximum induction efficiency of differentiation of hBMSCs into DA neurons was 91.67% in LXR+GF group. After the long-term use of TO901317, LXRα and LXRβ decreased significantly, and ABCA1mRNA increased significantly in LXR+GF group. After induced-cells were transplanted into PD rats, Compared with 6-OHDA group, the expression of TH in the striatum increased significantly, and the behavior of PD rats induced by apomorphine was significantly improved in the 6-OHDA+Cells group.Conclusions: TO901317 promoted differentiation of hBMSCs into DA neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggested that TO901317 may serve as a potential therapeutic methods for PD.


2020 ◽  
Vol 8 (A) ◽  
pp. 508-511
Author(s):  
Gusti Revilla ◽  
Henny Mulyani

BACKGROUND: Research on human bone marrow mesenchymal stem cells (hBM-MSCs) for burns healing has been known to increase the percentage of integrin expression of α2β1, type I collagen, transforming growth factor-β, and matrix metalloproteinases-9, but research on giving hBM-MSCs to growth factor expression in the process of re-epithelialization of burn healing has not been done. AIM: This study aims to the effect of hBM-MSCs given on the expression of epidermal growth factor (EGF) and EGF receptor (EGFR) in the process re-epithelialization in the healing of burn experimental rat. MATERIALS AND METHODS: This research is experimental with the post-test only control design, using 30 Wistar rats. Rats were divided into two groups, namely, control (phosphate-buffered saline), and the treatment was given hBM-MSCs, and stem cells were given subcutaneous doses of 2 × 106 cells/ml. Before being treated rats were anesthetized using xylazine and ketamine then the rats were burned in the dorsal (spine) with full-thickness. On the 3, 7, and 14 days, skin tissue was taken to see the expression of EGF and EGFR by immunohistochemical methods. This study was approved by the Ethics Commission of the Faculty of Medicine, Andalas University, Padang. The results of the study were analyzed by the t-test. RESULTS: Immunohistochemical examination of EGF and EGFR expressions after hBM-MSCs administration has significantly increased epithelialization compared with controls. Increased EGF expression was found on days 3 and 7 with moderate positive internal revenue service (IRS) assessment and on day 14 strong positive EGF expression, as well as EGFR expression on days 3 and 7 with moderate positive IRS assessment and on day 14 robust positive EGFR expression. CONCLUSION: This study concluded that giving of hBM-MSCs can increase the expression of EGF and EGFR which enhances the process of re-epithelialization thereby accelerating the healing of burns of experimental rats.


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