Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis. (30th June 2016)

• Record Type: Journal Article
• Authors: Jang, Yoon Ok; Cho, Mee-Yon; Yun, Chae-Ok; Baik, Soon Koo; Park, Kyu-Sang; Cha, Seung-Kuy; Chang, Sei Jin; Kim, Moon Young; Lim, Yoo Li; Kwon, Sang Ok
• Is Part Of: Stem cells translational medicine. Volume 5:Number 9(2016)
• Page Start: 1247
• Page End: 1256
• Publication Date: 2016-06-30
• Subjects: Mesenchymal stem cell -- Adenovirus -- Gene therapy -- Liver regeneration -- Transforming growth factor-β; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2015-0323
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract : A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Treatment with BM-MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis. Abstract : : Bone marrow-derived mesenchymal stem cells (BM-MSCs) are known to have an antifibrotic effect and could be used as vehicles for targeted gene delivery. Decorin plays a protective role against fibrogenesis by modulating the degradation of the extracellular matrix. The aim of this study was to determine whether the antifibrotic effect of a combination treatment consisting of BM-MSCs and decorin on hepatic fibrosis is superior to BM-MSCs alone. The effects of BM-MSCs infected with decorin-expressing adenovirus (DCN-MSCs) on hepatic fibrosis were examined in a rat model of thioacetamide (TAA)-induced cirrhosis. The effects of infection with decorin-expressing adenovirus and of incubation with the conditioned medium of DCN-MSCs on transforming growth factor- β (TGF- β ) signaling were analyzed in immortalized human hepatic stellate cells (HSCs). According to the Laennec fibrosis scoring system, cirrhotic livers from rats treated with DCN-MSCs exhibited histological improvement compared with cirrhotic livers from rats treated with control adenovirus-infected MSCs (CA-MSCs). DCN-MSC treatment reduced hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with DCN-MSCs than with CA-MSCs. The upregulation of collagen-1, α -smooth muscle actin ( α -SMA), TGF- β 1, and Smad3 phosphorylation in cirrhotic livers was prevented by DCN-MSC administration. Intriguingly, medium from cultured DCN-MSCs blocked both Smad3 phosphorylation and exogenous TGF- β 1 stimulated α -SMA synthesis in HSCs. DCN-MSCs exert strong protective effects against hepatic fibrosis by suppressing TGF- β /Smad signaling. Thus, treatment with DCN-MSCs is a potentially novel and efficient therapeutic approach for patients with intractable cirrhosis. Significance : A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Furthermore, the significant inhibitory effect of BM-MSCs infected with decorin-expressing adenovirus was attributed to suppressing transforming growth factor- β (TGF- β )/Smad signaling pathway, supported by attenuation of TGF- β 1 expression and inhibition of Smad3 phosphorylation. Therefore, treatment with BM-MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis.