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Nanofiber-expanded stem cells mitigate liver fibrosis: Experimental study
Institution:1. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of China;2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of China;3. The University of Chinese Academy of Sciences, Beijing, People’s Republic of China;4. Health Improving Department, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China;5. The First Hospital of Jilin University, Changchun, People’s Republic of China;1. Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, Health Sciences, University of Utah, Salt Lake City, UT, United States;2. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, United States;3. Institute of Advanced Biomedical Engineering and Science, Tokyo Women''s Medical University, Tokyo, Japan
Abstract:ObjectivesThis study examines a pretreatment strategy to strengthen the hepatic lineage divergence of mesenchymal stem cells (MSCs).Design and methodsBMSCs were expanded in the presence or absence of nanofiber (NF) and treated with growth factors (GF) prior to transplantation. Thioacetamide (TA) was used for liver fibrosis induction and transplantation of NF-expanded BMSCs was compared biochemically and histologically to the cells expanded without NF scaffold.ResultsThe ultraweb NF caused better proliferation and characterization of MSCs. MSCs transplantation significantly improved liver functions, increased hepatic HGF and Bcl-2 levels, whereas decreased serum fibronectin, hepatic TNF-α and TGF-β1 levels. Hepatic HNF4α, FOXa2, CYP7a1 genes expression were enhanced while β-5-Tub and AFP genes expression were depressed. Histological study documented these results. Differentiated NF-MSCs showed pronounced enhancement of the aforementioned parameters as compared to differentiated MSCs in the absence of NF.Conclusionpretreatment with growth factors in the presence of NF augment homing, repopulation and hepatic differentiation abilities of MSCs and proves to be a promising approach for the treatment of liver fibrosis.
Keywords:AFP  Bcl-2  Liver fibrosis  Mesenchymal stem cells  Rats  Scaffolds  TGF-β1  Ultraweb nanofiber
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