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Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats

Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of tran...

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Autores principales: Zhang, Ziqiang, Zhang, Mengyu, Sun, Yingying, Li, Monan, Chang, Chenhao, Liu, Weiqi, Zhu, Xuemin, Wei, Lan, Wen, Fengyun, Liu, Yumei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085980/
https://www.ncbi.nlm.nih.gov/pubmed/37037844
http://dx.doi.org/10.1038/s41598-023-32906-9
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author Zhang, Ziqiang
Zhang, Mengyu
Sun, Yingying
Li, Monan
Chang, Chenhao
Liu, Weiqi
Zhu, Xuemin
Wei, Lan
Wen, Fengyun
Liu, Yumei
author_facet Zhang, Ziqiang
Zhang, Mengyu
Sun, Yingying
Li, Monan
Chang, Chenhao
Liu, Weiqi
Zhu, Xuemin
Wei, Lan
Wen, Fengyun
Liu, Yumei
author_sort Zhang, Ziqiang
collection PubMed
description Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H(2)O(2) to establish an apoptosis model. The control, H(2)O(2) and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H(2)O(2)-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H(2)O(2) group. Compared with the H(2)O(2) group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.
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spelling pubmed-100859802023-04-12 Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats Zhang, Ziqiang Zhang, Mengyu Sun, Yingying Li, Monan Chang, Chenhao Liu, Weiqi Zhu, Xuemin Wei, Lan Wen, Fengyun Liu, Yumei Sci Rep Article Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H(2)O(2) to establish an apoptosis model. The control, H(2)O(2) and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H(2)O(2)-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H(2)O(2) group. Compared with the H(2)O(2) group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats. Nature Publishing Group UK 2023-04-10 /pmc/articles/PMC10085980/ /pubmed/37037844 http://dx.doi.org/10.1038/s41598-023-32906-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Ziqiang
Zhang, Mengyu
Sun, Yingying
Li, Monan
Chang, Chenhao
Liu, Weiqi
Zhu, Xuemin
Wei, Lan
Wen, Fengyun
Liu, Yumei
Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title_full Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title_fullStr Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title_full_unstemmed Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title_short Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
title_sort effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085980/
https://www.ncbi.nlm.nih.gov/pubmed/37037844
http://dx.doi.org/10.1038/s41598-023-32906-9
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