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A novel antifibrotic strategy utilizing conditioned media obtained from miR-150-transfected adipose-derived stem cells: validation of an animal model of liver fibrosis.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-03-09 , DOI: 10.1038/s12276-020-0393-1
Kwang Yeol Paik 1 , Kee-Hwan Kim 2, 3 , Jung Hyun Park 4 , Jae Im Lee 2 , Ok-Hee Kim 3, 5 , Ha-Eun Hong 5 , Haeyeon Seo 5 , Ho Joong Choi 5 , Joseph Ahn 5 , Tae Yun Lee 5 , Say-June Kim 3, 5
Affiliation  

The limitations of stem cells have led researchers to investigate the secretome, which is the secretory materials in stem cells, since the principal mechanism of action of stem cells is mediated by the secretome. In this study, we determined the antifibrotic potential of the secretome released from miR-150-transfected adipose-derived stromal cells (ASCs). The secretome released from ASCs that were transfected with antifibrotic miR-150 was obtained (referred to as the miR-150 secretome). To validate the antifibrotic effects of the miR-150 secretome, we generated in vitro and in vivo models of liver fibrosis by treating human hepatic stellate cells (LX2 cells) with thioacetamide (TAA) and subcutaneous injection of TAA into mice, respectively. In the in vitro model, more significant reductions in the expression of fibrosis-related markers, such as TGFβ, Col1A1, and α-SMA, were observed by using the miR-150 secretome than the control secretome, specifically in TAA-treated LX2 cells. In the in vivo model, infusion of the miR-150 secretome into mice with liver fibrosis abrogated the increase in serum levels of systemic inflammatory cytokines, such as IL-6 and TNF-α, and induced increased expression of antifibrotic, proliferation, and antioxidant activity markers in the liver. Our in vitro and in vivo experiments indicate that the miR-150 secretome is superior to the naive secretome in terms of ameliorating liver fibrosis, minimizing systemic inflammatory responses, and promoting antioxidant enzyme expression. Therefore, we conclude that miR-150 transfection into ASCs has the potential to induce the release of secretory materials with enhanced antifibrotic, proliferative, and antioxidant properties.

中文翻译:

一种新的抗纤维化策略,利用从miR-150转染的脂肪干细胞获得的条件培养基:肝纤维化动物模型的验证。

干细胞的局限性导致研究人员研究了分泌组,它是干细胞中的分泌物质,因为干细胞的主要作用机制是由分泌组介导的。在这项研究中,我们确定了从miR-150转染的脂肪基质细胞(ASC)中释放的分泌蛋白的抗纤维化潜力。获得了从转染了抗纤维化miR-150的ASC中释放的分泌物组(称为miR-150分泌物组)。为了验证miR-150分泌蛋白组的抗纤维化作用,我们分别通过用硫代乙酰胺(TAA)处理人肝星状细胞(LX2细胞)并向小鼠皮下注射TAA生成了肝纤维化的体外和体内模型。在体外模型中,与纤维化相关的标志物的表达更加显着降低,通过使用miR-150分泌组比对照分泌组观察到TGFβ,Col1A1和α-SMA等特异性受体,特别是在TAA处理的LX2细胞中。在体内模型中,向患有肝纤维化的小鼠输注miR-150分泌基因组可消除全身性炎性细胞因子(如IL-6和TNF-α)的血清水平增加,并诱导抗纤维化,增殖和抗氧化剂的表达增加肝脏中的活性标记。我们的体外和体内实验表明,在改善肝纤维化,最小化全身性炎症反应和促进抗氧化酶表达方面,miR-150分泌组优于天然分泌组。因此,我们得出的结论是,将miR-150转染到ASC中有潜力诱导分泌性物质的释放,增强抗纤维化,增殖,
更新日期:2020-04-24
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