Adipose derived stem cell conditioned medium effect on proliferation phase of wound healing in Sprague Dawley rat

Twidy Tarcisia, Lia Damayanti, Radiana D. Antarianto, Yefta Moenadjat, Jeanne A. Pawitan



Background: Disintegration of skin tissue can lead to disability and death. Recent studies on wound therapy applied stem cells and adipose derived stem cell conditioned medium (ADSC-CM) to improve wound healing. However, the role of ADSC-CM in wound healing mechanism in terms of angiogenesis, quantity of collagen, and epithelialization is not fully understood. Therefore, this study aimed to analyze the levels of growth factors (VEGF and EGF) in ADSC-CM and histological features of angiogenesis, epithelialization, and collagen density after skin incision in Sprague Dawley rats.

Methods: Thirty rats were injured at the back (full thickness wound) and treated topically with ADSC-CM, culture medium, basal medium, and without treatment. Mice were sacrificed on days 3, 7, 14, 21 and 28. After sacrificed, tissue samples were examined microscopically to assess angiogenesis, epithelialization, and collagen density. Concentrations of VEGF and EGF in ADSC-CM were measured by ELISA.

Results: Clinically, wound that was treated with ADSC-CM showed improvement in wound healing process. ADSC-CM treated wound showed the highest epithelialization ratio and the fastest wound closure.

Conclusion: There were no statistical significant differences between groups that were treated with ADSC-CM and not. However, topical ADSC-CM treated wound revealed a better clinical improvement in epithelialization.


ADSC-CM; angiogenesis; collagen density; epithelialization; wound healing

Full Text:



  1. Kondo T, Ishida Y. Molecular pathology of wound healing. Forensic Sci Int. 2010;203(1–3):93–8.
  2. Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI. Prevalensi cedera dan penyebabnya. In: Riset kesehatan dasar Riskesdas 2013. Jakarta; Kementerian Kesehatan RI:2013. p. 101. Indonesian.
  3. Dinh T, Braunagel S, Rosenblum BI. Growth factors in wound healing; the present and the future? Clin Podiatr Med Surg. 2015;32(1):109–19.
  4. Mirza RE, Koh TJ. Contributions of cell subsets to cytokine production during normal and impared wound healing. Cytokine. 2015;71(2):409–12.
  5. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29.
  6. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanism. J Int Med Res. 2009;37(5):1528–42.
  7. Harper D, Young A, Mc Naught C-E. The physiology of wound healing. Surgery. 2014;32:445–50.
  8. Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int. 2014;2014:965849.
  9. Lee SH, Jin SY, Song JS, Seo KK, Cho KH. Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Ann Dermatol. 2012;24(2):136–43.
  10. Walter MNM, Wright KT, Fuller HS, MacNeil S, Johnson WEB. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res. 2010;316:1271–81.
  11. Kim J, Lee JH, Yeo SM, Chung HM, Chae JI. Stem cell recruitment factors secreted from cord blood-derived stem cell that are not secreted from mature endothelial cells enhance wound healing. In Vitro Cell Dev Biol. 2014;50(2):146–54.
  12. Greaves NS, Ashcorft KJ, Baguneid M, Bayat A. Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. J Dermatol Sci. 2013;72(3):206–17.
  13. Chen D, Hao H, Fu X, Han W. Insight into reepithelialization: how do mesenchymal stem cells perform? Stem Cells Int. 2016;2016:6120173.
  14. Bellavia G, Fasanaro P, Melchionna R, Capogrossi MC, Napolitano M. Transcriptional control of skin reepithelialization. J Dermatol Sci. 2014;73(1):3–9.
  15. Bielefeld KA, Amini-Nik S, Alman BA. Cutaneous wound healing: recruiting developmental pathways for regeneration. Cell Mol Life Sci. 2013;70(12):2059–81.
  16. Santoro MM, Gaudino G. Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp Cell Res. 2005;304(1):274–86.
  17. Kwon SH, Bhang SH, Jang HK, Rhim T, Kim BS. Conditioned medium of adipose-derived stromal cell culture in three-dimensional bioreactors for enhanced wound healing. J Surg Res. 2015;194(1):8–17.
  18. Bhang SH, Lee S, Shin JY, Lee TJ, Jang HK, Kim BS. Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. Mol Ther. 2014;22(4):862–72.
  19. She T, Hu D, Zhang J, Zhang W, Liu J, Chen G, et al. Cytobiological effect of adipose-derived stem cells treated with insulin on HaCat cells. Zhonqquo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009;23(6):727–31.
  20. Park BS, Kim WS, Choi JS, Kim HK, Won JH, Ohkubo F, et al. Hair growth stimulation by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion. Biomed Res. 2010;31(1):27–34.
  21. Kryger Z, Zhang F, Dogan T, Cheng C, Lineaweaver WC, Buncke HJ. The effects of VEGF on survival of a random flap in the rat: exaination of various routes of adminitration. Br J Plast Surg. 2000;53(3):234–9.
  22. Rohani MG, Parks WC. Matrix remodeling by MMPs during wound repair. Matrix Biol. 2015;44–46:113–21.
  23. Hu L, Zhao J, Liu J, Gong N, Chen L. Effects of adipose stem cell-conditioned medium on the migration of vascular endothelial cells, fibroblasts and keratinocytes. Exp Ther Med. 2013;5:701–6.

Copyright (c) 2018 twidy tarcisia

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

All articles and issues in Medical Journal of Indonesia have unique DOI number registered in Crossref.
Unique Visitors