Role of Exosomes Derived from Secretome Human Umbilical Vein Endothelial Cells (Exo-HUVEC) as Anti-Apoptotic, Anti-Oxidant, and Increasing Fibroblast Migration in Photoaging Skin Models


  • Endra Yustin Ellistasari Department of Doctoral Program of Medical Sciences, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Harijono Kariosentono Department of Dermatology and Venereology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Bambang Purwanto Department of Internal Medicine, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Brian Wasita Department of Anatomical Pathology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Risya Cilmiaty Arief Riswiyant Department of Dentistry, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Eti Poncorini Pamungkasari Department of Public Health, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia
  • Soetrisno Soetrisno Department of Obstetric and Gynecology, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia



Exo-HUVEC, Fibroblast migration, MDA, PI/Annexin


Background: Prolonged skin exposure to ultraviolet light rays leads to photoaging, which is characterized molecularly by an increase in reactive oxygen species (ROS), cell apoptosis, and a decrease in collagen. Photoaging therapy has been a challenge until recently. Fibroblasts exposed to ultraviolet B (UVB) light proved to be a good model for photoaging skin. They are also the primary dermal cells that stimulate collagen production and extracellular matrix (ECM), which contribute to skin aging. Exo-HUVEC is rich in growth factors, cytokines, and miRNAs, and they all play a vital role in cell-to-cell communication. The migration of fibroblasts is crucial for the development, repair, and regeneration of skin tissue during the repair of skin aging.

Objective: An in vitro experimental study was conducted to analyze the effect of Exo-HUVEC on oxidative stress levels, cell apoptosis, and fibroblast migration rate after UVB ray exposure on fibroblasts.

Methods: The fibroblast cultures were divided into five groups, including one without UVB exposure, one with UVB exposure, and one with UVB+Exo-HUVEC exposure at 0.1%, 0.5%, and 1%, respectively. Oxidative stress levels were measured using the ELISA test for malondialdehyde (MDA). Furthermore, flow cytometry was used to measure apoptosis using PI/Annexin markers, while a scratch assay examination was used to measure fibroblast migration rate using imaging readings.

Results: There were significant differences in the levels of MDA, PI/Annexin, and the rate of fibroblast migration between the UVB-irradiated control group and the Exo-HUVEC treatment group (p<0.001).

Conclusion: Exo-HUVEC is a marker of photoaging improvement, which has anti-apoptotic effects and reduces oxidative stress, as well as increases fibroblast migration rate.


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Babizhayev MA. Treatment of skin aging and photoaging with innovative oral dosage forms of non-hydrolized carnosine and carcinine. Int J Clin Dermatol Res. 2017;5(5):116-43. DOI:

Tobin DJ. Introduction to skin aging. J Tissue Viability. 2017;26(1):37-46. PMid:27020864 DOI:

Zouboulis CC, Makrantonaki E, Nikolakis G. When the skin is in the center of interest: An aging issue. Clin Dermatol. 2019;37(4):296-305. PMid:31345316 DOI:

Samuel M, Brooke R, Hollis S, Griffiths CE. Interventions for photodamaged skin. Cochrane Database Syst Rev. 2015;2015(6):CD001782. PMid:26035235 DOI:

Glass GE. Cosmeceuticals: The principles and practice of skin rejuvenation by non-prescription topical therapy. Aesthet Surg J Open Forum. 2020;2(4):38. DOI:

Ayer J, Griffiths CE. Photoaging in Caucasians. Ch. 1. 2019. p. 1-30. Available from: [Last accessed on 2022 Mar 28]. DOI:

Lee CH, Wu SB, Hong CH, Yu HS, Wei YH. Molecular mechanisms of UV-induced apoptosis and its effects on skin residential cells: The implication in UV-based phototherapy. Int J Mol Sci. 2013;14(3):6414-35. https://doi./org/10.3390/ijms14036414 PMid:23519108 DOI:

Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR. Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. J Vis Exp. 2011;50:2597. PMid:21540825 DOI:

Duensing TD, Watson SR. Assessment of apoptosis (Programmed cell death) by flow cytometry. Cold Spring Harb Protoc. 2018;2018(1):93807. PMid:29295901 DOI:

Gary AS, Rochette PJ. Apoptosis, the only cell death pathway that can be measured in human diploid dermal fibroblasts following lethal UVB irradiation. Sci Rep. 2020;10(1):18946. PMid:33144600 DOI:

Hardiany NS, Sucitra S, Paramita R. Profile of malondialdehyde (MDA) and catalase specific activity in plasma of elderly woman. Heal Sci J Indones. 2020;10(2):132-6. DOI:

Medina-Leyte DJ, Domínguez-Pérez M, Mercado I, Villarreal- Molina MT, Jacobo-Albavera L. Use of human umbilical vein endothelial cells (HUVEC) as a model to study cardiovascular disease: A review. Appl Sci. 2020;10(3):938. DOI:

Rudt A, Sun J, Qin M, Liu L, Syldatk C, Barbeck M, et al. Controlled adhesion of HUVEC on polyelectrolyte multilayers by regulation of coating conditions. ACS Appl Bio Mater. 2020;4(2):1441-9. PMid:35014494 DOI:

Zhao D, Yu Z, Li Y, Wang Y, Li Q, Han D. GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration. J Mol Histol. 2020;51(3):251-63. DOI:

Tanaka K, Asamitsu K, Uranishi H, Iddamalgoda A, Ito K, Kojima H, et al. Protecting skin photoaging by NF-κB inhibitors. Curr Drug Metab. 2010;11(54):431-5. PMid:20540695 DOI:

Guo SC, Tao SC, Yin WJ, Qi X, Yuan T, Zhang CQ. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics. 2017;7(1):81-96. PMid:28042318 DOI:

Williams JD, Bermudez Y, Park SL, Stratton SP, Uchida K, Hurst CA, et al. Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue. J Photochem Photobiol B. 2014;132:56-65. PMid:24584085 DOI:

Jun Z, Wen DA, Jing Z, Jia Z, Zhi CA. Protective effect of anti-aging Klotho protein on human umbilical vein endothelial cells treated with high glucose. Chin J Pathophysiol. 2017;33:67-72.

Kendall TR, Feghali-Bostwick AC. Fibroblasts in fibrosis: novel roles and mediators. Front Pharm. 2014:5:123. PMid:24904424 DOI:

Piipponen M, Li D, Landén XN. The immune functions of keratinocytes in skin wound healing. Int J Mol Sci. 2020;21(22):8790. PMid:33233704 DOI:

Liu X, Zhang R, Shi H, Li X, Li Y, Taha A, et al. Protective effect of curcumin against ultraviolet A irradiationinduced photoaging in human dermal fibroblasts. Mol Med Rep. 2018;17(5):7227-37. PMid:29568864 DOI:

Sahin F, Koçak P, Güneş MY, Kan Z, Yıldırım E, Kala EY. In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles. Appl Biochem Biotechnol. 2019;188(2):381-94. Available from: [Last accessed on 2022 Apr 01]. DOI:

Wirohadidjojo YW, Budiyanto A, Soebono H. Platelet-Rich Fibrin Lysate Can Ameliorate Dysfunction of Chronically UVA-Irradiated Human Dermal Fibroblast. Yonsei Med J. 2016;57(5):1282. PMid:27401663 DOI:

Aioi A. Inflammaging in skin and intrinsic underlying factors. Trends Immunother. 2021;5(2):44-53. DOI:

Oh M, Lee J, Kim Y, Rhee W, Park J. Eksosom berasal dari sel punca pluripoten terinduksi manusia memperbaiki penuaan fibroblas kulit. Int J Mol Sci. 2018;19(6):1715. Available from: DOI:

Hwang S, Lee PC, Shin DM, Hong JH. Modulated start-up mode of cancer cell migration through spinophilin-tubular networks. Front Cell Develop Biol. 2021;9:652791. PMid:33768098 DOI:

Zhang H, Wang Y, Bai M, Wang J, Zhu K, Liu R, et al. Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Science. 2018;109(3):629-41. Available from: [Last accessed on 2022 Apr 03]. DOI:

Peres PS, Terra VA, Guarnier FA, Cecchini R, Cecchini AL. Photoaging and chronological aging profile: Understanding oxidation of the skin. J Photochem Photobiol B. 2011;103(2):93-7. PMid:21356598 DOI:

Shen C, Lie P, Miao T, Yu M, Lu Q, Feng T, et al. Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis. Mole Med Rep. 2015;12(1):20-30. PMid:25739039 DOI:

Kim YJ, Yoo SM, Park HH, Lim HJ, Kim YL, Lee S, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem Biophys Res Commun. 2017;493(2):1102-8. PMid:28919421 DOI:

Jimenez N, Krouwer VJ, Post JA. A new, rapid and reproducible method to obtain high quality endothelium in vitro. Cytotechnology. 2013;65(1):1-14. PMid:22573289 DOI:

Bodega G, Alique M, Puebla L, Carracedo J, Ramírez RM. Microvesicles: ROS scavengers and ROS producers. J Extracell Vesicles. 2019;8(1):1626654. .2019.1626654 PMid:31258880 DOI:




How to Cite

Ellistasari EY, Kariosentono H, Purwanto B, Wasita B, Riswiyant RCA, Pamungkasari EP, Soetrisno S. Role of Exosomes Derived from Secretome Human Umbilical Vein Endothelial Cells (Exo-HUVEC) as Anti-Apoptotic, Anti-Oxidant, and Increasing Fibroblast Migration in Photoaging Skin Models. Open Access Maced J Med Sci [Internet]. 2022 Jun. 23 [cited 2023 Mar. 28];10(A):1193-9. Available from:

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