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Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

Reactive oxygen species (ROS)-associated oxidative stress, inflammation storm, and massive hepatocyte necrosis are the typical manifestations of acute liver failure (ALF), therefore specific therapeutic interventions are essential for the devastating disease. Here, we developed a platform consisting...

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Autores principales: Jin, Yuanyuan, Zhang, Jiabin, Xu, Yanteng, Yi, Ke, Li, Fenfang, Zhou, Huicong, Wang, Haixia, Chan, Hon Fai, Lao, Yeh-Hsing, Lv, Shixian, Tao, Yu, Li, Mingqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209199/
https://www.ncbi.nlm.nih.gov/pubmed/37250866
http://dx.doi.org/10.1016/j.bioactmat.2023.05.001
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author Jin, Yuanyuan
Zhang, Jiabin
Xu, Yanteng
Yi, Ke
Li, Fenfang
Zhou, Huicong
Wang, Haixia
Chan, Hon Fai
Lao, Yeh-Hsing
Lv, Shixian
Tao, Yu
Li, Mingqiang
author_facet Jin, Yuanyuan
Zhang, Jiabin
Xu, Yanteng
Yi, Ke
Li, Fenfang
Zhou, Huicong
Wang, Haixia
Chan, Hon Fai
Lao, Yeh-Hsing
Lv, Shixian
Tao, Yu
Li, Mingqiang
author_sort Jin, Yuanyuan
collection PubMed
description Reactive oxygen species (ROS)-associated oxidative stress, inflammation storm, and massive hepatocyte necrosis are the typical manifestations of acute liver failure (ALF), therefore specific therapeutic interventions are essential for the devastating disease. Here, we developed a platform consisting of versatile biomimetic copper oxide nanozymes (Cu NZs)-loaded PLGA nanofibers (Cu NZs@PLGA nanofibers) and decellularized extracellular matrix (dECM) hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells (hADMSCs-derived HLCs) (HLCs/Cu NZs@fiber/dECM). Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF, and reduce the massive accumulation of pro-inflammatory cytokines, herein efficiently preventing the deterioration of hepatocytes necrosis. Moreover, Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted HLCs. Meanwhile, HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy. The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs. In addition, the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host liver. Hence, HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF mice. This strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.
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spelling pubmed-102091992023-05-26 Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure Jin, Yuanyuan Zhang, Jiabin Xu, Yanteng Yi, Ke Li, Fenfang Zhou, Huicong Wang, Haixia Chan, Hon Fai Lao, Yeh-Hsing Lv, Shixian Tao, Yu Li, Mingqiang Bioact Mater Article Reactive oxygen species (ROS)-associated oxidative stress, inflammation storm, and massive hepatocyte necrosis are the typical manifestations of acute liver failure (ALF), therefore specific therapeutic interventions are essential for the devastating disease. Here, we developed a platform consisting of versatile biomimetic copper oxide nanozymes (Cu NZs)-loaded PLGA nanofibers (Cu NZs@PLGA nanofibers) and decellularized extracellular matrix (dECM) hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells (hADMSCs-derived HLCs) (HLCs/Cu NZs@fiber/dECM). Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF, and reduce the massive accumulation of pro-inflammatory cytokines, herein efficiently preventing the deterioration of hepatocytes necrosis. Moreover, Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted HLCs. Meanwhile, HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy. The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs. In addition, the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host liver. Hence, HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF mice. This strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation. KeAi Publishing 2023-05-18 /pmc/articles/PMC10209199/ /pubmed/37250866 http://dx.doi.org/10.1016/j.bioactmat.2023.05.001 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Jin, Yuanyuan
Zhang, Jiabin
Xu, Yanteng
Yi, Ke
Li, Fenfang
Zhou, Huicong
Wang, Haixia
Chan, Hon Fai
Lao, Yeh-Hsing
Lv, Shixian
Tao, Yu
Li, Mingqiang
Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title_full Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title_fullStr Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title_full_unstemmed Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title_short Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
title_sort stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209199/
https://www.ncbi.nlm.nih.gov/pubmed/37250866
http://dx.doi.org/10.1016/j.bioactmat.2023.05.001
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