scholarly journals Combination therapy of Juzentaihoto and mesenchymal stem cells attenuates liver damage and regresses fibrosis in mice

2021 ◽  
Vol 18 ◽  
pp. 231-241
Author(s):  
Takahiro Iwasawa ◽  
Shunsuke Nojiri ◽  
Atsunori Tsuchiya ◽  
Suguru Takeuchi ◽  
Takayuki Watanabe ◽  
...  
2020 ◽  
Vol 41 (5) ◽  
pp. 1069-1078
Author(s):  
Parisa Ramhormozi ◽  
Javad Mohajer Ansari ◽  
Sara Simorgh ◽  
Maliheh Nobakht

Abstract Burn wound healing is one of the most important problems in the field of medical science. Promising results have recently been reported by researchers who used bone marrow mesenchymal stem cells (BMSCs) to treat burn wounds. In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats. After creating second-degree burn wounds, 40 adult male Wistar rats were randomly divided into four treatment groups: the control, SMV, BMSCs, and the combination therapy group (BMSCs+SMV). Animals were killed 14 days after treatment initiation, and the wounds were removed for histological and molecular analyses. All in all, combination therapy produced better outcomes than individual therapy in terms of the wound closure area, epidermal regeneration level, collagen deposition intensity, and reepithelialization rate. In addition, the elevations of expression levels of Akt and mTOR genes, at both mRNA and protein levels, were more pronounced in the BMSCs+SMV group (P < .05, at least, for both qRT-PCR and western blot assessments). qRT-PCR findings also demonstrated that the wounds treated with the combination of BMSCs and SMV had the highest expression levels of CD31 and VEGF genes (P < .01 for all comparisons). These data suggest that the combined administration of BMSCs transplantation and topical SMV has a great potential in burn wound healing. According to the findings, the beneficial effects of the combination therapy are caused, at least in part, through stimulating Akt/mTOR signaling pathway.


2014 ◽  
Vol 29 (2) ◽  
pp. 540-553 ◽  
Author(s):  
Brooke M. Huuskes ◽  
Andrea F. Wise ◽  
Alison J. Cox ◽  
Ee X. Lim ◽  
Natalie L. Payne ◽  
...  

2022 ◽  
Author(s):  
Rui Zhang ◽  
Wenhang Li ◽  
Xiandan Jiang ◽  
Xinyi Cui ◽  
Hongjie You ◽  
...  

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) are effective for treating fibrotic liver. BMSCs contain a variety of proteins and RNAs, which have functions similar to their derived cells, but the specific mechanism is unclear. In a recent study, ferulic acid (FA) was highly effective in treating liver fibrosis. Therefore, we combined BMSCs and FA to treat CCl4-induced fibrosis models. Methods: First, we used BMSCs and FA to treat CCl4-induced fibrosis models and observed their therapeutic effect, investigated the specific mechanism of this combination therapy in liver fibrosis. Second, we created a BMSC/hepatic stellate cell (HSC) co-culture system and used FA to treat activated HSCs. We next used cytochalasin D and angiotensin II to investigate whether BMSCs and FA inactivate HSCs through cytoskeletal rearrangement. MiR-19b-3p was enriched in BMSCs and targeted TGF-β receptor II (TGF-βR2). We transfected miR-19b-3p into HSCs and BMSCs separately and detected whether BMSCs transferred miR-19b-3p to HSCs or inactivated HSCs. Results: We used BMSCs and FA to treat CCl4-induced fibrosis models and found that the combination therapy had better effects than FA or BMSCs alone. The expression of the profibrotic markers α-SMA and COL1-A1 was significantly decreased in HSCs co-cultured with BMSCs and FA treatment. Cytoskeletal rearrangement in HSCs was inhibited, and RhoA/ROCK pathway gene expression was decreased. With angiotensin II treatment, COL1-A1 and a-SMA expression increased, while with cytochalasin D treatment, profibrotic gene expression decreased in HSCs. COL1-A1, α-SMA and RhoA/ROCK pathway genes were decreased in activated HSCs treated with a miR-19b-3p mimic, indicating that miR-19b-3p inactivated HSCs by suppressing RhoA/ROCK signalling. In contrast, profibrotic genes were significantly decreased in BMSCs treated with the miR-19b-3p mimic or a miR-19b-3p inhibitor and FA compared with BMSCs treated with the miR-19b-3p mimic alone.Conclusion: BMSCs attenuated HSC activation and liver fibrosis by inhibiting cytoskeletal rearrangement and delivering miR-19b-3p to activated HSCs, inactivating RhoA/ROCK signaling. FA-based combination therapy showed better inhibitory effects on HSC activation, suggesting that BMSCs and their miRNAs combined with FA are novel antifibrotic therapeutics for treating chronic liver disease.


2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Francisca Alcayaga-Miranda ◽  
Jimena Cuenca ◽  
Aldo Martin ◽  
Luis Contreras ◽  
Fernando E. Figueroa ◽  
...  

Life Sciences ◽  
2009 ◽  
Vol 85 (13-14) ◽  
pp. 517-525 ◽  
Author(s):  
Yao-Jen Chang ◽  
Jen-Wea Liu ◽  
Po-Cheng Lin ◽  
Li-Yi Sun ◽  
Chih-Wen Peng ◽  
...  

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