DOI: https://doi.org/10.14710/jbtr.v12i2.28892

Hypoxia-Induced Mesenchymal Stem Cell Exosomes Promote PDGF and IL-10 Expression During Burn Wound Healing

1Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Indonesia

21 Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung, Indonesia

32 Department of Surgery, Faculty of Medicine, Universitas Islam Sultan Agung, Indonesia

4 Department of Anatomy, Faculty of Medicine, Universitas Islam Sultan Agung, Indonesia

View all affiliations
Received: 11 Aug 2025; Revised: 20 Mar 2026; Accepted: 13 Apr 2026; Available online: 29 Aug 2026; Published: 31 Aug 2026.
Open Access Copyright (c) 2026 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:
Abstract

Background: Burn injuries remain a global health concern, with third-degree burns posing high morbidity and mortality risks. Effective wound healing requires both regeneration and inflammation control. Hypoxia-induced mesenchymal stem cell-derived exosomes (EH-MSCs) have emerged as a promising cell-free therapy due to their regenerative and immunomodulatory properties.

Objective: This study aimed to evaluate the effect of EH-MSCs on the expression of Platelet-Derived Growth Factor (PDGF) and Interleukin-10 (IL-10) in a Wistar rat model of third-degree burns.

Methods: An experimental study with a Post-Test Only Control Group design was conducted at the Stem Cell and Cancer Research Laboratory, Sultan Agung Islamic University, Semarang, in April 2025. Thirty male Wistar rats (6–8 weeks, 200–250 g) were randomized into five groups: healthy control, burn + NaCl, burn + silver sulfadiazine, burn + EH-MSC 100 µg/mL, and burn + EH-MSC 200 µg/mL. Third-degree burns were induced using a 2 × 2 cm² pre-heated metal plate under ether anesthesia. EH-MSCs were isolated from rat umbilical cords using tangential flow filtration and validated with CD63 and CD9 markers. On day 5, PDGF and IL-10 expressions were measured via RT-PCR after orbital sinus blood sampling. Data were analyzed using Shapiro-Wilk and Levene’s tests, followed by One-Way ANOVA or non-parametric equivalents, with p<0.05 considered significant.

Results: PDGF and IL-10 expression increased in EH-MSC-treated groups, with the highest levels in the 200 µg/mL dose. IL-10 showed a significant difference among groups (p = 0.030), and post hoc tests confirmed higher expression in EH-MSC groups. PDGF showed a significant pairwise difference, though overall ANOVA was not significant (p = 0.094).

Conclusion: EH-MSCs significantly enhanced IL-10 expression and increased PDGF levels, supporting their potential to promote regeneration and modulate inflammation in burn wound healing.

Note: This article has supplementary file(s).

Fulltext View|Download |  Research Instrument
Cover Letter
Subject
Type Research Instrument
  Download (15KB)    Indexing metadata
 Research Instrument
List of Potential Reviewer
Subject
Type Research Instrument
  Download (15KB)    Indexing metadata
 Research Instrument
Copyright Transfer Agreement (CTA)
Subject
Type Research Instrument
  Download (1MB)    Indexing metadata
Email colleagues
Keywords: burn wound; mesenchymal stem cells; exosomes; PDGF; IL-10

Article Metrics:

Article Info
Section: Original Research Articles
Language : EN
  1. World Health Organization. Burns [Internet]. World Health Organization (WHO). 2023 [cited 2025 Aug 5]. Available from: https://www.who.int/news-room/fact-sheets/detail/burns
  2. Wardhana A, Basuki A, Prameswara ADH, Rizkita DN, Andarie AA, Canintika AF. The epidemiology of burns in Indonesia’s national referral burn center from 2013 to 2015. Burn Open [Internet]. 2017 Oct;1(2):67–73. Available from: https://linkinghub.elsevier.com/retrieve/pii/S246891221730038X. doi: 10.1016/j.burnso.2017.08.002
  3. Lestari T, Syukur S, Revilla G, Sukma Rita R, Rustini R. The Burn Wound Healing Process : A Review. Int J Progress Sci Technol [Internet]. 2023 Aug 18;40(1):77. Available from: https://ijpsat.org/index.php/ijpsat/article/view/5565. doi: 10.52155/ijpsat.v40.1.5565
  4. Jiang H, Zhao H, Zhang M, He Y, Li X, Xu Y, et al. Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects. Front Immunol [Internet]. 2022 Apr 4;13. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2022.824188/full. doi: 10.3389/fimmu.2022.824188
  5. Cui G, Wu J, Mou F, Xie W, Wang F, Wang Q, et al. Exosomes derived from hypoxia‐preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J [Internet]. 2018 Feb 4;32(2):654–68. Available from: https://onlinelibrary.wiley.com/doi/abs/ 10.1096/fj.201700600R doi: 10.1096/fj.201700600R
  6. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet‐derived growth factor in wound healing. J Cell Biochem [Internet]. 1991 Apr 19;45(4):319–26. Available from: https://onlinelibrary.wiley.com/doi/ 10.1002/jcb.240450403 doi: 10.1002/jcb.240450403
  7. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic‐Canic M. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing. Wound Repair Regen [Internet]. 2008 Sep 3;16(5):585–601. Available from: https://onlinelibrary.wiley.com/doi/ 10.1111/j.1524-475X.2008.00410.x doi: 10.1111/j.1524-475X.2008.00410.x
  8. Sun ZL, Feng Y, Zou ML, Zhao BH, Liu SY, Du Y, et al. Emerging Role of IL-10 in Hypertrophic Scars. Front Med [Internet]. 2020 Aug 27;7. Available from: https://www.frontiersin.org/article/10.3389/fmed.2020.00438/full. doi: 10.3389/fmed.2020.00438
  9. Iyer SS, Cheng G. Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease. Crit Rev Immunol [Internet]. 2012;32(1):23–63. Available from: http://www.dl.begellhouse.com/journals/2ff21abf44b19838,76944bab5ddebfc1,2a93e3a12bdb71e5.html. doi: 10.1615/CritRevImmunol.v32.i1.30
  10. Dirja BT, Wardoyo EH, Putra A, Amalina ND. Enhanced Third Degree Burn Wound Healing by Hypoxic Mesenchymal Stem Cells’ Secretome: IL-10 Upregulation and TNF-α/PGE2 Suppression. Trends Sci [Internet]. 2024 Sep 30;21(10):8288. Available from: https://tis.wu.ac.th/index.php/tis/article/view/8288. doi: 10.48048/tis.2024.8288
  11. Kazlauskas A. PDGFs and their receptors. Gene [Internet]. 2017 May;614:1–7. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0378111917301385. doi: 10.1016/j.gene.2017.03.003
  12. Folestad E, Kunath A, Wågsäter D. PDGF-C and PDGF-D signaling in vascular diseases and animal models. Mol Aspects Med [Internet]. 2018 Aug;62:1–11. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0098299717301097. doi: 10.1016/j.mam.2018.01.005
  13. Lu K, Wu C, Bao J. Molecular modeling, expression and wound-repair activity in vivo of platelet-derived growth factor from Periplaneta americana. Process Biochem [Internet]. 2021 Nov;110:151–62. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1359511321002506. doi: 10.1016/j.procbio.2021.08.009
  14. Zhou C, Zhang B, Yang Y, Jiang Q, Li T, Gong J, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. Stem Cell Res Ther [Internet]. 2023 Apr 26;14(1):107. Available from: https://stemcellres.biomedcentral.com/articles/ 10.1186/s13287-023-03345-0 doi: 10.1186/s13287-023-03345-0
  15. Verma R, Balakrishnan L, Sharma K, Khan AA, Advani J, Gowda H, et al. A network map of Interleukin-10 signaling pathway. J Cell Commun Signal [Internet]. 2016 Mar;10(1):61–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26253919. doi: 10.1007/s12079-015-0302-x
  16. Liu L, Yu Y, Hou Y, Chai J, Duan H, Chu W, et al. Human Umbilical Cord Mesenchymal Stem Cells Transplantation Promotes Cutaneous Wound Healing of Severe Burned Rats. Covas DT, editor. PLoS One [Internet]. 2014 Feb 20;9(2):e88348. Available from: https://dx.plos.org/ 10.1371/journal.pone.0088348 doi: 10.1371/journal.pone.0088348
  17. Casado-Díaz A, Quesada-Gómez JM, Dorado G. Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing. Front Bioeng Biotechnol [Internet]. 2020 Mar 3;8. Available from: https://www.frontiersin.org/article/10.3389/fbioe.2020.00146/full. doi: 10.3389/fbioe.2020.00146
  18. Haraszti RA, Miller R, Stoppato M, Sere YY, Coles A, Didiot MC, et al. Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity. Mol Ther [Internet]. 2018 Dec;26(12):2838–47. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1525001618304568. doi: 10.1016/j.ymthe.2018.09.015
  19. Wallace HA, Basehore BM, Zito PM. Wound Healing Phases [Internet]. StatPearls. 2025. Available from: http://www.ncbi.nlm.nih.gov/pubmed/0
  20. Żwierełło W, Piorun K, Skórka-Majewicz M, Maruszewska A, Antoniewski J, Gutowska I. Burns: Classification, Pathophysiology, and Treatment: A Review. Int J Mol Sci. 2023 Feb 13;24(4):3749. . doi: 10.3390/ijms24043749
  21. Yang G, Waheed S, Wang C, Shekh M, Li Z, Wu J. Exosomes and Their Bioengineering Strategies in the Cutaneous Wound Healing and Related Complications: Current Knowledge and Future Perspectives. Int J Biol Sci [Internet]. 2023;19(5):1430–54. Available from: https://www.ijbs.com/v19p1430.htm. doi: 10.7150/ijbs.80430
  22. Novello S, Pellen‐Mussi P, Jeanne S. Mesenchymal stem cell‐derived small extracellular vesicles as cell‐free therapy: Perspectives in periodontal regeneration. J Periodontal Res [Internet]. 2021 Jun 28;56(3):433–42. Available from: https://onlinelibrary.wiley.com/doi/ 10.1111/jre.12866 doi: 10.1111/jre.12866
  23. Liao Z, Zheng R, Shao G. Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review). Int J Mol Med [Internet]. 2022 Dec 5;51(1):7. Available from: http://www.spandidos-publications.com/ 10.3892/ijmm.2022.5210 doi: 10.3892/ijmm.2022.5210
  24. Winkler I, Engler JB, Vieira V, Bauer S, Liu YH, Di Liberto G, et al. MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration. Sci Adv [Internet]. 2023 Nov 24;9(47). Available from: https://www.science.org/doi/ 10.1126/sciadv.adi6855 doi: 10.1126/sciadv.adi6855

Last update:

No citation recorded.

Last update:

No citation recorded.