Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus, often leading to severe outcomes. Given the limitations of current treatments, other strategies are needed to address this gap. Recently, the administration of hypoxia-conditioned mesenchymal stem cells (HC-MSC)...

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Main Authors: Nur Anna Chalimah Sadyah, Heri-Nugroho, Agung Putra, Ignatius Riwanto
Format: Article
Language:English
Published: International Medical Research and Development Corporation 2025-03-01
Series:International Journal of Biomedicine
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Online Access:http://www.ijbm.org/articles/i57/ijbm_15(1)_oa4.pdf
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author Nur Anna Chalimah Sadyah
Heri-Nugroho
Agung Putra
Ignatius Riwanto
author_facet Nur Anna Chalimah Sadyah
Heri-Nugroho
Agung Putra
Ignatius Riwanto
author_sort Nur Anna Chalimah Sadyah
collection DOAJ
description Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus, often leading to severe outcomes. Given the limitations of current treatments, other strategies are needed to address this gap. Recently, the administration of hypoxia-conditioned mesenchymal stem cells (HC-MSC) secretome has shown promise in treating DFUs, particularly in improving wound healing. This study aims to evaluate the efficacy of HC-MSC-derived secretome gel in treating DFUs by assessing its impact on inflammatory biomarkers, specifically IL-10 and NF-κB p65 gene expression. Methods and Results: This randomized, prospective, controlled clinical trial included 16 patients with type 2 diabetes mellitus (T2DM) and Grade 2–3 DFUs. A control group (n=8) was treated with a placebo/base gel, and an intervention group was treated with HC-MSC-derived secretome gel produced by the Stem Cell and Cancer Research Center, Indonesia. The clinical wound volume, IL-10, and NF-κB p65 were assessed pre- and post-treatment. The relative quantification (RQ) of IL-10 showed a significant increase in the intervention group on Day 7 after treatment compared to the placebo group (mean difference of 1.12, P<0.001), indicating an enhanced anti-inflammatory response. The RQ of NF-κB p65 gene expression significantly decreased in the intervention group (mean difference of 0.488, P=0.001), suggesting reduced inflammatory signaling. These results correlate with improved wound healing in the intervention group, evidenced by reductions in wound volume (mean difference of 0.826 cm3, P=0.002) on Day 7 after treatment. Conclusion: HC-MSC-derived secretome gel significantly enhanced IL-10 expression and reduced NF-κB p65 gene expression in DFUs, improving wound healing outcomes. This approach shows promise as an alternative to conventional treatments. Further research is needed to understand the mechanisms involved.
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spelling doaj-art-5fd45f044b7c41d6b85c4e6dfb1fbf052025-08-20T03:05:42ZengInternational Medical Research and Development CorporationInternational Journal of Biomedicine2158-05102158-05292025-03-01151788310.21103/Article15(1)_OA4Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial Nur Anna Chalimah Sadyah0 Heri-Nugroho1Agung Putra2Ignatius Riwanto3Doctoral Study Program of Medical and Health Science, Universitas Diponegoro, Semarang, Indonesia; Department of Internal Medicine, Sultan Agung Islamic Hospital, Semarang, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, IndonesiaDepartment of Internal Medicine, Faculty of Medicine, Universitas Diponegoro, Semarang, IndonesiaStem Cell and Cancer Research, Semarang, Indonesia; Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Semarang, IndonesiaDepartment of Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, IndonesiaBackground: Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus, often leading to severe outcomes. Given the limitations of current treatments, other strategies are needed to address this gap. Recently, the administration of hypoxia-conditioned mesenchymal stem cells (HC-MSC) secretome has shown promise in treating DFUs, particularly in improving wound healing. This study aims to evaluate the efficacy of HC-MSC-derived secretome gel in treating DFUs by assessing its impact on inflammatory biomarkers, specifically IL-10 and NF-κB p65 gene expression. Methods and Results: This randomized, prospective, controlled clinical trial included 16 patients with type 2 diabetes mellitus (T2DM) and Grade 2–3 DFUs. A control group (n=8) was treated with a placebo/base gel, and an intervention group was treated with HC-MSC-derived secretome gel produced by the Stem Cell and Cancer Research Center, Indonesia. The clinical wound volume, IL-10, and NF-κB p65 were assessed pre- and post-treatment. The relative quantification (RQ) of IL-10 showed a significant increase in the intervention group on Day 7 after treatment compared to the placebo group (mean difference of 1.12, P<0.001), indicating an enhanced anti-inflammatory response. The RQ of NF-κB p65 gene expression significantly decreased in the intervention group (mean difference of 0.488, P=0.001), suggesting reduced inflammatory signaling. These results correlate with improved wound healing in the intervention group, evidenced by reductions in wound volume (mean difference of 0.826 cm3, P=0.002) on Day 7 after treatment. Conclusion: HC-MSC-derived secretome gel significantly enhanced IL-10 expression and reduced NF-κB p65 gene expression in DFUs, improving wound healing outcomes. This approach shows promise as an alternative to conventional treatments. Further research is needed to understand the mechanisms involved.http://www.ijbm.org/articles/i57/ijbm_15(1)_oa4.pdfdiabetes mellitusmesenchymal stem cellil-10p65wound healing
spellingShingle Nur Anna Chalimah Sadyah
Heri-Nugroho
Agung Putra
Ignatius Riwanto
Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
International Journal of Biomedicine
diabetes mellitus
mesenchymal stem cell
il-10
p65
wound healing
title Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
title_full Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
title_fullStr Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
title_full_unstemmed Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
title_short Hypoxia-Conditioned Mesenchymal Stem Cells (HC-MSC)-Derived Secretome Gel Induce IL-10 to Improve Diabetic Foot Ulcers via Reduced NF-κB p65 Gene Expression: A Randomized Controlled Trial
title_sort hypoxia conditioned mesenchymal stem cells hc msc derived secretome gel induce il 10 to improve diabetic foot ulcers via reduced nf κb p65 gene expression a randomized controlled trial
topic diabetes mellitus
mesenchymal stem cell
il-10
p65
wound healing
url http://www.ijbm.org/articles/i57/ijbm_15(1)_oa4.pdf
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