1116 https://www.id-press.eu/mjms/index Scientifc Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Oct 30; 8(B):1116-1123. https://doi.org/10.3889/oamjms.2020.5305 eISSN: 1857-9655 Category: B - Clinical Sciences Section: Ophtalmology Topical Instillation of Resveratrol Preconditioned Wharton’s Jelly Mesenchymal Stem Cell Secretome Preserves Ocular Surface in Experimental Model of Severe Dry Eye Disease Diandra Astaridewi 1 , Evelyn Komaratih 1 , Yuyun Rindiastuti 1 , Yohanes Widodo Wirohadidjojo 2 , Djoko Legowo 3 , Ni Made Inten Lestari 1 , Diandra Astari Dewi 1 , I. Made Satya 1 , Fedik A. Rantam 4 , Cita R. S. Prakoeswa 5 * 1 Department of Ophthalmology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia; 2 Department of Dermatovenerology, Faculty of Medicine, Universitas Gadjah Mada, Dr. Sardjito General Academic Hospital, Radioputro Building, Yogyakarta, Indonesia; 3 Department of Pathology Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Kampus C Mulyorejo, Surabaya, Indonesia; 4 Stem Cell Research and Development Center, Universitas Airlangga, Tropical Disease Center Building, Kampus C Mulyorejo, Surabaya, Indonesia; 5 Department of Dermatovenerology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia Abstract BACKGROUND: Secretome derived from Wharton’s jelly mesenchymal stem cells (WJ-MSC) has a benefcial efect for ocular surface regeneration; however, the high amount of vascular endothelial growth factor (VEGF) remains a challenge for its application. AIM: The aim of the study was to investigate the efect of resveratrol (RV) (VEGF reducing agent) preconditioned WJ-MSC secretome in Concanavalin A-induced severe dry eye model. METHODS: Pre- and post-experimental study composed of topical instillation of WJ-MSC secretome group, balanced salt solution control group, and normal control group. Tear production, tear break-up time (TBUT), corneal fuorescein dye staining, VEGF level in aqueous tear, goblet cell density, and infammatory cells in the ocular surface were analyzed. RESULTS: Topical instillation of RV preconditioned WJ-MSC secretome successfully improved tear flm production (p = 0.008) and TBUT (p = 0.008), promoted goblet cell restoration (p = 0.023) and reduced corneal fuorescein staining (p = 0.003), while inhibited infltration of infammatory cells (p = 0.01) and secretion of VEGF in aqueous tear (p = 0.003). CONCLUSION: Topical instillation of RV preconditioned WJ-MSC secretome has great potential as cell-free based therapy to preserve ocular surface in an experimental model of severe Dry eye disease. Edited by: Ksenija Bogoeva-Kostovska Citation: Astaridewi D, Komaratih E, Rindiastuti Y, Wirohadidjojo YW, Legowo D, Lestari NMI, Dewi DA, Satya IM, Rantam FA, Prakoeswa CRS. Topical Instillation of Resveratrol Preconditioned Wharton’s Jelly Mesenchymal Stem Cell Secretome Preserves Ocular Surface in Experimental Model of Severe Dry Eye Disease. Open Access Maced J Med Sci. 2020 Oct 30; 8(B):1116-1123. https://doi.org/10.3889/oamjms.2020. 5305 Keywords: Mesenchymal stem cell; Resveratrol; Secretome; Dry eye disease; Ocular surface *Correspondence: Cita R.S Prakoeswa, Department of Dermatovenerology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya. Jl. Mayjen. Prof. Dr. Moestopo 4-7, Surabaya, 60132. E-mail: cita-rosita@fk.unair.ac.id Received: 24-Jul-2020 Revised: 15-Oct-2020 Accepted: 19-Oct-2020 Copyright: © 2020 Diandra Astaridewi, Evelyn Komaratih, Yuyun Rindiastuti, Yohanes Widodo Wirohadidjojo, Djoko Legowo, Ni Made Inten Lestari, Diandra Astari Dewi, I. Made Satya, Fedik A. Rantam, Cita R. S. Prakoeswa Funding: This research did not receive any fnancial support Competing Interests: The authors have declared that no competing interests exist Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC 4.0) Introduction Dry eye disease (DED) is an important public health problem that could hinder the performance of daily living activities, and therefore decreases the quality of life [1], [2] The infammatory process in accordance with downregulation of growth factors such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), and keratinocyte growth factor, while increasing of vascular endothelial growth factor (VEGF) leads to ocular surface damage in DED. VEGF-A, member of the cysteine superfamily plays a key role in corneal neovascularization [3], [4], [5], [6]. The mainstay therapy for DED is the application of artifcial tears and topical anti-infammatory or immunosuppressant that provides additional lubrication for the ocular surface and improves the symptoms of chronic infammation. However, limited results and adverse ocular efects have been reported. In recent years, regenerative therapy has emerged a new strategy that promises an improvement in the management of DED [1], [2], [7]. Wharton’s jelly mesenchymal stem cells (WJ-MSC) are multipotent stem cells with the ability to diferentiate into many mesoderm cell lineages. Investigation of MSC to treat immune-mediated disease has gained encouraging results [1], [2]. MSC transplantation has raised exciting expectations in