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

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 Ul...

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Autores principales: Xu, Yi-Feng, Wu, Yan-Xiang, Wang, Hong-Mei, Gao, Cui-Hua, Xu, Yang-Yang, Yan, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040509/
https://www.ncbi.nlm.nih.gov/pubmed/36948071
http://dx.doi.org/10.1016/j.clinsp.2023.100181
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author Xu, Yi-Feng
Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
author_facet Xu, Yi-Feng
Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
author_sort Xu, Yi-Feng
collection PubMed
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.
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spelling pubmed-100405092023-03-28 Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats Xu, Yi-Feng Wu, Yan-Xiang Wang, Hong-Mei Gao, Cui-Hua Xu, Yang-Yang Yan, Yang Clinics (Sao Paulo) Original Articles 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. Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo 2023-03-20 /pmc/articles/PMC10040509/ /pubmed/36948071 http://dx.doi.org/10.1016/j.clinsp.2023.100181 Text en © 2023 HCFMUSP. Published by Elsevier España, S.L.U. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Articles
Xu, Yi-Feng
Wu, Yan-Xiang
Wang, Hong-Mei
Gao, Cui-Hua
Xu, Yang-Yang
Yan, Yang
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
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_short 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
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040509/
https://www.ncbi.nlm.nih.gov/pubmed/36948071
http://dx.doi.org/10.1016/j.clinsp.2023.100181
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