Skip to main content
SpringerLink
Log in

Effectiveness of Mesenchymal Stem Cell Secretome on Wound Healing: A Systematic Review and Meta-analysis

  • Review Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis on the effectiveness of secretome in promoting wound healing.

Methods:

To ensure the rigor and transparency of our study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, as registered in PROSPERO with ID: CRD42023412671. We conducted a comprehensive search on four electronic databases to identify studies evaluating the effect of secretome on various clinical parameters of wound repair. In addition, we evaluated the risk of bias for each study using the Jadad and Newcastle-Ottawa scale. To synthesize the data, we employed a fixed-effects model and calculated the mean difference or odds ratio (OR) with a 95% confidence interval (CI).

Results:

Based on six included articles, secretome is known to affect several clinical parameters in wound healing included the size and depth of ulcers during healing; the E´chelle d’évaluation clinique des cicatrices d’acne (ECCA) score, epidermal thickness, collagen fibers, abnormal elastic tissues, volume of atrophic acne scars, skin pore volume, and erythema during acne scar healing; and microcrust areas, erythema index, transepidermal water loss, volume of atrophic acne scars, erythema, and relative gene expression of procollagen type I, procollagen type III, and elastin were evaluated in wound healing after laser treatment. Meta-analysis studies showed that secretome reduced ulcer size (mean difference: 0.87, 95% CI of 0.37–1.38, p = 0.0007), decreased ulcer depth (mean difference: 0.18, 95% CI of 0.11–0.25, p < 0.00001), and provided patient satisfaction (odds ratio: 9.71, 95% CI of 3.47–21.17, p < 0.0001). However, secretome failed to reach significance in clinical improvement (OR 0.38, 95% CI 0.10, 1.53, p = 0.06).

Conclusion:

The secretome provides good effectiveness in accelerating wound healing through a mechanism that correlates with several clinical parameters of wound repair.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wound Assessment. Available online: https://www.ncbi.nlm.nih.gov/books/NBK482198/. Accessed 31 Oct 2022.

  2. Afonso AC, Oliveira D, Saavedra MJ, Borges A, Simões M. Biofilms in diabetic foot ulcers: impact, risk factors and control strategies. Int J Mol Sci. 2021;22:8278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wound Classification. Available online: https://www.ncbi.nlm.nih.gov/books/NBK554456/. Accessed 31 Oct 2022.

  4. Larouche J, Sheoran S, Maruyama K, Martino MM. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv Wound Care. 2018;7:209–31.

    Article  Google Scholar 

  5. Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of acute and chronic wound healing. Biomolecules. 2021;11:700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther. 2017;34:599–610.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Brumberg V, Astrelina T, Malivanova T, Samoilov A. Modern wound dressings: hydrogel dressings. Biomedicines. 2021;9:1235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Monika P, Chandraprabha MN, Rangarajan A, Waiker PV, Murthy KNC. Challenges in healing wound: role of complementary and alternative medicine. Front Nutr. 2022;8:791899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sood A, Granick MS, Tomaselli NL. Wound dressings and comparative effectiveness data. Adv Wound Care. 2014;3:511–29.

    Article  Google Scholar 

  10. Kanji S, Das H. Advances of stem cell therapeutics in cutaneous wound healing and regeneration. Mediat Inflamm. 2017;2017:5217967.

    Article  CAS  Google Scholar 

  11. Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022;7:272.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Oliveira PH, da Silva CL, Cabral JM. Concise review: genomic instability in human stem cells: current status and future challenges. Stem Cells. 2014;32:2824–32.

    Article  CAS  PubMed  Google Scholar 

  13. Ibrahim R, Mndlovu H, Kumar P, Adeyemi SA, Choonara YE. Cell secretome strategies for controlled drug delivery and wound-healing applications. Polymers. 2022;14:2929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. González-González A, García-Sánchez D, Dotta M, Rodríguez-Rey JC, Pérez-Campo FM. Mesenchymal stem cells secretome: the cornerstone of cell-free regenerative medicine. World J Stem Cells. 2020;12:1529–52.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18:1852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ahangar P, Mills SJ, Cowin AJ. Mesenchymal stem cell secretome as an emerging cell-free alternative for improving wound repair. Int J Mol Sci. 2020;21:7038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pokrovskaya LA, Zubareva EV, Nadezhdin SV, Lysenko AS, Litovkina TL. Biological activity of mesenchymal stem cells secretome as a basis for cell-free therapeutic approach. Res Results Pharmacol. 2020;6:57–68.

    Article  CAS  Google Scholar 

  18. Guo X, Schaudinn C, Blume-Peytavi U, Vogt A, Rancan F. Effects of adipose-derived stem cells and their conditioned medium in a human ex vivo wound model. Cells. 2022;11:1198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bartaula-Brevik S, Bolstad A, Mustafa K, Pedersen TO. Secretome of mesenchymal stem cells grown in hypoxia accelerates wound healing and vessel formation in vitro. Int J Stem Cell Res Ther. 2017;4. https://doi.org/10.23937/2469-570X/1410045

    Article  Google Scholar 

  20. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906.

    Article  PubMed  Google Scholar 

  21. Olivo SA, Macedo LG, Gadotti IC, Fuentes J, Stanton T, Magee DJ. Scales to assess the quality of randomized controlled trials: a systematic review. Phys Ther. 2008;88:156–75.

    Article  PubMed  Google Scholar 

  22. Lo CK, Mertz D, Loeb M. Newcastle-Ottawa scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol. 2014;14:45.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Oremus M, Wolfson C, Perrault A, Demers L, Momoli F, Moride Y. Interrater reliability of the modified Jadad quality scale for systematic reviews of Alzheimer’s disease drug trials. Dement Geriatr Cogn Disord. 2001;12:232–6.

    Article  CAS  PubMed  Google Scholar 

  24. Margulis AV, Pladevall M, Riera-Guardia N, Varas-Lorenzo C, Hazell L, Berkman N, et al. Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa scale and the RTI item bank. Clin Epidemiol. 2014;6:359–68.

    Article  PubMed  PubMed Central  Google Scholar 

  25. The Nordic Cochrane Centre. Review Manager, Version 5.4; The Cochrane Collaboration: Copenhagen, Denmark, 2020.

  26. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Wiley; 2019.

    Book  Google Scholar 

  27. Alinda MD, Christopher PM, Listiawan MY, Endaryanto A, Suroto H, Rantam FA, et al. Comparative efficacy of topical adipocyte-derived mesenchymal stem cells-conditioned medium (Admsc-cm) and amniotic membrane mesenchymal stem cells-conditioned medium (amsc-cm) on chronic plantar ulcers in leprosy: a randomized controlled trial. Bali Med J. 2021;10:958–63.

    Article  Google Scholar 

  28. Kim J, Kim B, Kim S, Lee YI, Kim J, Lee JH. The effect of human umbilical cord blood-derived mesenchymal stem cell media containing serum on recovery after laser treatment: a double-blinded, randomized, split-face controlled study. J Cosmet Dermatol. 2020;19:651–6.

    Article  PubMed  Google Scholar 

  29. Abdel-Maguid EM, Awad SM, Hassan YS, El-Mokhtar MA, El-Deek HE, Mekkawy MM. Efficacy of stem cell-conditioned medium vs. platelet-rich plasma as an adjuvant to ablative fractional CO2 laser resurfacing for atrophic post-acne scars: a split-face clinical trial. J Dermatol Treat. 2021;32:242–9.

    Article  CAS  Google Scholar 

  30. El-Domyati M, Moftah NH, Nasif GA, Ragaie MH, Ibrahim MR, Ameen SW. Amniotic fluid-derived mesenchymal stem cell products combined with microneedling for acne scars: a split-face clinical, histological, and histometric study. J Cosmet Dermatol. 2019;18:1300–6

    Article  PubMed  Google Scholar 

  31. Park CS, Park JH, Kim CR, Lee JH. Objective analysis of volume restoration in atrophic acne scars and skin pores: a split study using human stem cell-conditioned media. J Dermatol Treat. 2021;32:73–7.

    Article  CAS  Google Scholar 

  32. Zhou BR, Xu Y, Guo SL, Xu Y, Wang Y, Zhu F, et al. The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing. Biomed Res Int. 2013;2013:519126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Fife D. Practical evaluation and management of atrophic acne scars: tips for the general dermatologist. J Clin Aesthet Dermatol. 2011;4:50–7.

    PubMed  PubMed Central  Google Scholar 

  34. Gozali MV, Zhou B. Effective treatments of atrophic acne scars. J Clin Aesthet Dermatol. 2015;8:33–40.

    PubMed  PubMed Central  Google Scholar 

  35. Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous scarring: basic science, current treatments, and future directions. Adv Wound Care. 2018;7:29–45.

    Article  Google Scholar 

  36. Chilicka K, Rusztowicz M, Szyguła R, Nowicka D. Methods for the Improvement of acne scars used in dermatology and cosmetology: a review. J Clin Med. 2022;11:2744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fan H, Zhang JW, Liu DJ, Liu FB. Transepidermal water loss of scar skin in three types of scar patients and its correlation with scar severity. Zhonghua Shao Shang Za Zhi. 2021;37:629–34.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to express their gratitude to the Rector of Universitas Padjadjaran for providing funding for this study. Additionally, they would like to extend their appreciation to the Deanship of Scientific Research at Northern Border University in Arar, Kingdom of Saudi Arabia, for generously funding this research through project number “NBU-FFR-2023-0065.”

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia

    Cecep Suhandi & Nasrul Wathoni

  2. Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt

    Ahmed Fouad Abdelwahab Mohammed

  3. Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia

    Gofarana Wilar

  4. Department of Chemistry, Faculty of Science, Northern Border University, Arar, Saudi Arabia

    Ali El-Rayyes

Authors
  1. Cecep Suhandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed Fouad Abdelwahab Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gofarana Wilar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali El-Rayyes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nasrul Wathoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CS, NW, AFAM and AER participated in performing research and data analysis, CS initially written the original draft, CS, NW, AFAM and AER also participated in reviewing and editing final manuscript, GW participated in supervising and taking final decision of issues.

Corresponding author

Correspondence to Nasrul Wathoni.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest in this manuscript.

Ethical statement

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 46 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suhandi, C., Mohammed, A.F.A., Wilar, G. et al. Effectiveness of Mesenchymal Stem Cell Secretome on Wound Healing: A Systematic Review and Meta-analysis. Tissue Eng Regen Med 20, 1053–1062 (2023). https://doi.org/10.1007/s13770-023-00570-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-023-00570-9

Keywords

Search

Navigation