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A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice

Intracerebral hemorrhage (ICH) poses a great threat to human health because of its high mortality and morbidity. Neural stem cell (NSC) transplantation is promising for treating white matter injury following ICH to promote functional recovery. However, reactive oxygen species (ROS)‐induced NSC apopt...

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Autores principales: Lei, Xuejiao, Hu, Quan, Ge, Hongfei, Zhang, Xuyang, Ru, Xufang, Chen, Yujie, Hu, Rong, Feng, Hua, Deng, Jun, Huang, Yan, Li, Wenyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013746/
https://www.ncbi.nlm.nih.gov/pubmed/36925711
http://dx.doi.org/10.1002/btm2.10451
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author Lei, Xuejiao
Hu, Quan
Ge, Hongfei
Zhang, Xuyang
Ru, Xufang
Chen, Yujie
Hu, Rong
Feng, Hua
Deng, Jun
Huang, Yan
Li, Wenyan
author_facet Lei, Xuejiao
Hu, Quan
Ge, Hongfei
Zhang, Xuyang
Ru, Xufang
Chen, Yujie
Hu, Rong
Feng, Hua
Deng, Jun
Huang, Yan
Li, Wenyan
author_sort Lei, Xuejiao
collection PubMed
description Intracerebral hemorrhage (ICH) poses a great threat to human health because of its high mortality and morbidity. Neural stem cell (NSC) transplantation is promising for treating white matter injury following ICH to promote functional recovery. However, reactive oxygen species (ROS)‐induced NSC apoptosis and uncontrolled differentiation hindered the effectiveness of the therapy. Herein, we developed a single‐cell nanogel system by layer‐by‐layer (LbL) hydrogen bonding of gelatin and tannic acid (TA), which was modified with a boronic ester‐based compound linking triiodothyronine (T3). In vitro, NSCs in nanogel were protected from ROS‐induced apoptosis, with apoptotic signaling pathways downregulated. This process of ROS elimination by material shell synergistically triggered T3 release to induce NSC differentiation into oligodendrocytes. Furthermore, in animal studies, ICH mice receiving nanogels performed better in behavioral evaluation, neurological scaling, and open field tests. These animals exhibited enhanced differentiation of NSCs into oligodendrocytes and promoted white matter tract regeneration on Day 21 through activation of the αvβ3/PI3K/THRA pathway. Consequently, transplantation of LbL(T3) nanogels largely resolved two obstacles in NSC therapy synergistically: low survival and uncontrolled differentiation, enhancing white matter regeneration and behavioral performance of ICH mice. As expected, nanoencapsulation with synergistic effects would efficiently provide hosts with various biological benefits and minimize the difficulty in material fabrication, inspiring next‐generation material design for tackling complicated pathological conditions.
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spelling pubmed-100137462023-03-15 A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice Lei, Xuejiao Hu, Quan Ge, Hongfei Zhang, Xuyang Ru, Xufang Chen, Yujie Hu, Rong Feng, Hua Deng, Jun Huang, Yan Li, Wenyan Bioeng Transl Med Research Articles Intracerebral hemorrhage (ICH) poses a great threat to human health because of its high mortality and morbidity. Neural stem cell (NSC) transplantation is promising for treating white matter injury following ICH to promote functional recovery. However, reactive oxygen species (ROS)‐induced NSC apoptosis and uncontrolled differentiation hindered the effectiveness of the therapy. Herein, we developed a single‐cell nanogel system by layer‐by‐layer (LbL) hydrogen bonding of gelatin and tannic acid (TA), which was modified with a boronic ester‐based compound linking triiodothyronine (T3). In vitro, NSCs in nanogel were protected from ROS‐induced apoptosis, with apoptotic signaling pathways downregulated. This process of ROS elimination by material shell synergistically triggered T3 release to induce NSC differentiation into oligodendrocytes. Furthermore, in animal studies, ICH mice receiving nanogels performed better in behavioral evaluation, neurological scaling, and open field tests. These animals exhibited enhanced differentiation of NSCs into oligodendrocytes and promoted white matter tract regeneration on Day 21 through activation of the αvβ3/PI3K/THRA pathway. Consequently, transplantation of LbL(T3) nanogels largely resolved two obstacles in NSC therapy synergistically: low survival and uncontrolled differentiation, enhancing white matter regeneration and behavioral performance of ICH mice. As expected, nanoencapsulation with synergistic effects would efficiently provide hosts with various biological benefits and minimize the difficulty in material fabrication, inspiring next‐generation material design for tackling complicated pathological conditions. John Wiley & Sons, Inc. 2022-11-16 /pmc/articles/PMC10013746/ /pubmed/36925711 http://dx.doi.org/10.1002/btm2.10451 Text en © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Lei, Xuejiao
Hu, Quan
Ge, Hongfei
Zhang, Xuyang
Ru, Xufang
Chen, Yujie
Hu, Rong
Feng, Hua
Deng, Jun
Huang, Yan
Li, Wenyan
A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title_full A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title_fullStr A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title_full_unstemmed A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title_short A redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
title_sort redox‐reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10013746/
https://www.ncbi.nlm.nih.gov/pubmed/36925711
http://dx.doi.org/10.1002/btm2.10451
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