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Review
. 2025 Feb 4:102:100778.
doi: 10.1016/j.curtheres.2025.100778. eCollection 2025.

The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies

Cecep Suhandi  1 , Gofarana Wilar  2 , Khaled M Elamin  3 , Audry Rahma Dewayani  1 , Salsabil Ghaliya  1 , Astriani Abdullah  1 , Nasrul Wathoni  1
Affiliations
Review

The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies

Cecep Suhandi et al. Curr Ther Res Clin Exp. .

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.

Keywords: Diabetic wound; Secretome; Stem cell; Wound healing.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image, graphical abstract
Graphical abstract
Fig 1
Figure 1
Flowchart of the study selection process.
Fig 2
Figure 2
Wound closure rate comparison between the stem cell secretome and control groups using a forest plot.
Fig 3
Figure 3
Number of fibroblasts comparison between the stem cell secretome and control groups using a forest plot.
Fig 4
Figure 4
Number of neutrophils comparison between the stem cell secretome and control groups using a forest plot.
Fig 5
Figure 5
Number of macrophages comparison between the stem cell secretome and control groups using a forest plot.
Fig 6
Figure 6
Publication bias with regard to wound closure rate interpretated by Egger's regression test.
See this image and copyright information in PMC

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