Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Detalhes bibliográficos
Autor(a) principal: Xu, Yi-Feng
Data de Publicação: 2023
Outros Autores: Wu, Yan-Xiang, Wang, Hong-Mei, Gao, Cui-Hua, Xu, Yang-Yang, Yan, Yang
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Clinics
Texto Completo: https://www.revistas.usp.br/clinics/article/view/213710
Resumo: Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.
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spelling Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in ratsDiabetic Foot UlcersConditioned-MediumMesenchymal Stem CellsTherapyObjectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2023-03-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/21371010.1016/j.clinsp.2023.100181Clinics; Vol. 78 (2023); 100181Clinics; v. 78 (2023); 100181Clinics; Vol. 78 (2023); 1001811980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/213710/195831Copyright (c) 2023 Clinicsinfo:eu-repo/semantics/openAccessXu, Yi-FengWu, Yan-XiangWang, Hong-MeiGao, Cui-HuaXu, Yang-YangYan, Yang2023-07-06T13:05:38Zoai:revistas.usp.br:article/213710Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2023-07-06T13:05:38Clinics - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
title Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
spellingShingle Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
Xu, Yi-Feng
Diabetic Foot Ulcers
Conditioned-Medium
Mesenchymal Stem Cells
Therapy
title_short Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
title_full Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
title_fullStr Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
title_full_unstemmed Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
title_sort Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats
author Xu, Yi-Feng
author_facet Xu, Yi-Feng
Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
author_role author
author2 Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Xu, Yi-Feng
Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
dc.subject.por.fl_str_mv Diabetic Foot Ulcers
Conditioned-Medium
Mesenchymal Stem Cells
Therapy
topic Diabetic Foot Ulcers
Conditioned-Medium
Mesenchymal Stem Cells
Therapy
description Objectives: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. Methods: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1β, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. Results: After the treatment wound area rate, IL-1β by ELISA, and IL-1β, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. Conclusions: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.
publishDate 2023
dc.date.none.fl_str_mv 2023-03-20
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/clinics/article/view/213710
10.1016/j.clinsp.2023.100181
url https://www.revistas.usp.br/clinics/article/view/213710
identifier_str_mv 10.1016/j.clinsp.2023.100181
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/clinics/article/view/213710/195831
dc.rights.driver.fl_str_mv Copyright (c) 2023 Clinics
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2023 Clinics
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
dc.source.none.fl_str_mv Clinics; Vol. 78 (2023); 100181
Clinics; v. 78 (2023); 100181
Clinics; Vol. 78 (2023); 100181
1980-5322
1807-5932
reponame:Clinics
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Clinics
collection Clinics
repository.name.fl_str_mv Clinics - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||clinics@hc.fm.usp.br
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