{"title":"The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies","authors":"Cecep Suhandi MSc , Gofarana Wilar PhD , Khaled M. Elamin PhD , Audry Rahma Dewayani BSc , Salsabil Ghaliya BSc , Astriani Abdullah BSc , Nasrul Wathoni PhD","doi":"10.1016/j.curtheres.2025.100778","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.</div></div><div><h3>Objective</h3><div>We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.</div></div><div><h3>Methods</h3><div>The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the <em>I²</em> statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.</div></div><div><h3>Results</h3><div>Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; <em>P</em> = 0.01, I<sup>2</sup> = 76%) and reduced the number of neutrophils (SMD = −8.47; 95% CI = −13.05 to −3.90; <em>P</em> = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; <em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100778"},"PeriodicalIF":1.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Therapeutic Research-clinical and Experimental","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0011393X25000037","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.
Objective
We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.
Methods
The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the I² statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.
Results
Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; P = 0.01, I2 = 76%) and reduced the number of neutrophils (SMD = −8.47; 95% CI = −13.05 to −3.90; P = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; P = 0.006).
Conclusion
This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.
期刊介绍:
We also encourage the submission of manuscripts presenting preclinical and very preliminary research that may stimulate further investigation of potentially relevant findings, as well as in-depth review articles on specific therapies or disease states, and applied health delivery or pharmacoeconomics.
CTR encourages and supports the submission of manuscripts describing:
• Interventions designed to understand or improve human health, disease treatment or disease prevention;
• Studies that focus on problems that are uncommon in resource-rich countries;
• Research that is "under-published" because of limited access to monetary resources such as English language support and Open Access fees (CTR offers deeply discounted English language editing);
• Republication of articles previously published in non-English journals (eg, evidence-based guidelines) which could be useful if translated into English;
• Preclinical and clinical product development studies that are not pursued for further investigation based upon early phase results.