scholarly journals Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

2020 ◽  
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dopamine Neurons ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 8

Abstract Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We 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 the previous work did not verify whether the induced cells had the corresponding neural function. Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression. Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. 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. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum. Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.

scholarly journals Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

2020 ◽  
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dopamine Neurons ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 8

Abstract Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We 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 the previous work did not verify whether the induced cells had the corresponding neural function. Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression. Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. 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. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum. Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.

Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease

1995 ◽  
Vol 1 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Hldeichi Takayama ◽  
Jasodhara Ray ◽  
Heather K. Raymon ◽  
Andrew Baird ◽  
Joanna Hogg ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Graft Survival ◽  
Basic Fibroblast Growth Factor ◽  
Rat Model ◽  
Fibroblast Growth ◽  
And Function

scholarly journals Plasma Concentrations of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Lymphoproliferative Disorders

2005 ◽  
Vol 48 (1) ◽  
pp. 57-58 ◽  
Author(s):  
Lukáš Smolej ◽  
Ctirad Andrýs ◽  
Vladimír Maisnar ◽  
Luděk Pour ◽  
Jaroslav Malý
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Endothelial Growth Factor

Angiogenesis plays a major role in the development and progression of haematological malignancies. In our study we measured plasma concentrations of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) using comercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 37 patients with lymphoid malignancies and 20 healthy donors. We found a statistically significant increase in bFGF concentrations in patients with B-cell chronic lymphocytic leukemia (B-CLL, n=18) compared to the control group (median 118.8 vs. 9.3 pg/ml, p<0.001). However, we didn’t find any significant difference in VEGF concentrations between B-CLL patients and the control group. There was also no significant increase in bFGF or VEGF in patients with multiple myeloma (n=7) and non-Hodgkin’s lymphoma (n=12). Our pilot study shows that measurement of angiogenic activators in plasma is a feasible and reproducible method of angiogenesis assessment. Larger studies are needed for correlation between serum and plasma concentrations and detailed statistical evaluation including the impact on patients’ survival.

scholarly journals The Effect of MSCs Derived from the Human Umbilical Cord Transduced by Fibroblast Growth Factor-20 on Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Li Jinfeng ◽  
Wang Yunliang ◽  
Liu Xinshan ◽  
Wang Shanshan ◽  
Xu Chunyang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Cell Therapy ◽  
Fibroblast Growth Factor ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Fibroblast Growth ◽  
Mice Model ◽  
Factor 20

Cell therapy is a potential therapeutic approach for Parkinson’s disease (PD). Mesenchymal stem cells derived from the human umbilical cord (hUC-MSCs) give priority to PD patients because of multiple advantages. The appropriate gene transduction of hUC-MSC before transplantation is a promising procedure for cell therapy. Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro. In this study, the hUC-MSCs were gene transduced with FGF-20, and then we transplanted them into the PD mice model. The results showed that MSC-FGF-20 treatment obviously improved the behavior of PD, accompanied by the increase of tyrosine carboxylase- (TH-) positive cell and dopamine (DA). Furtherly, immunohistochemistry disclosed that MSC-FGF-20 obviously promoted the degradation of nuclear factor-κB (NF-κB), a transcription factor that controls genes encoding proinflammatory cytokines, highly expressed in the nigrostriatal dopaminergic regions in PD patients. Therefore, MSC-FGF-20 has a potential for improving PD, closely related to the degradation of NF-κB.

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 ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Fibroblast Growth ◽  
Marrow Mesenchymal Stem Cells

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.

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