Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784906840604147712 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10013746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT leixuejiao aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT huquan aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT gehongfei aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT zhangxuyang aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT ruxufang aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT chenyujie aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT hurong aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT fenghua aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT dengjun aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT huangyan aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT liwenyan aredoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT leixuejiao redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT huquan redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT gehongfei redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT zhangxuyang redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT ruxufang redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT chenyujie redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT hurong redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT fenghua redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT dengjun redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT huangyan redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice AT liwenyan redoxreactivedeliverysystemvianeuralstemcellnanoencapsulationenhanceswhitematterregenerationinintracerebralhemorrhagemice |