標題: Enhanced Antioxidant Capacity of Dental Pulp-Derived iPSC-Differentiated Hepatocytes and Liver Regeneration by Injectable HGF-Releasing Hydrogel in Fulminant Hepatic Failure
作者: Chiang, Chih-Hung
Wu, Wai-Wah
Li, Hsin-Yang
Chien, Yueh
Sun, Cho-Chin
Peng, Chi-Hsien
Lin, Alex Tong-Long
Huang, Chi-Shuan
Lai, Ying-Hsiu
Chiou, Shih-Hwa
Hung, Shuen-Iu
Chang, Yuh-Lih
Lan, Yuan-Tzu
Liu, Dean-Mo
Chien, Chian-Shiu
Huo, Teh-Ia
Lee, Shou-Dong
Wang, Chien-Ying
材料科學與工程學系
Department of Materials Science and Engineering
關鍵字: Hydrogel;Induced pluripotent stem cells (iPSCs);Hepatocyte growth factor (HGF);Acute hepatic failure (AHF)
公開日期: 1-Jan-2015
摘要: Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF CHC) and investigated the hepatoprotective activity of HGF CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF CHC iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.
URI: http://dx.doi.org/10.3727/096368915X686986
http://hdl.handle.net/11536/124741
ISSN: 0963-6897
DOI: 10.3727/096368915X686986
期刊: CELL TRANSPLANTATION
Volume: 24
Issue: 3
起始頁: 541
結束頁: 559
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