Therapeutic Effect of Stem Cell Eye Drops on Dry Eye Disease

Summary

The goal of this non-randomized, prospective, open, one-arm clinical study is to learn about the clinical efficacy of stem cell eye drops in patients with dry eye disease (DED) who failed to respond to artificial tear sodium hyaluronate eye drops three times a day for two weeks. The main question aims to answer are: * How effective are stem cell eye drops in patients with DED? * How safe are stem cell eye drops for patients with DED? Participants will be treated with mesenchymal stem cells (MSCs) eye drops, 5×10\^5 /50μl in each eye, twice a day for two weeks and they will be followed up for three months after treatment.

Timeline

Start

2023-09-01

Primary completion

2028-07-31

Completion

2028-10-31

Publications

• Results Dana R, Bradley JL, Guerin A, Pivneva I, Stillman IO, Evans AM, Schaumberg DA. Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System. Am J Ophthalmol. 2019 Jun;202:47-54. doi: 10.1016/j.ajo.2019.01.026. Epub 2019 Feb 2.
• Results Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J, Viso E, Vitale S, Jones L. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017 Jul;15(3):334-365. doi: 10.1016/j.jtos.2017.05.003. Epub 2017 Jul 20.
• Results Pflugfelder SC, de Paiva CS. The Pathophysiology of Dry Eye Disease: What We Know and Future Directions for Research. Ophthalmology. 2017 Nov;124(11S):S4-S13. doi: 10.1016/j.ophtha.2017.07.010.
• Results Oguz H. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012 May;153(5):1003; author reply 1003-4. doi: 10.1016/j.ajo.2012.01.017. No abstract available.
• Results Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008 Nov;86(7):716-26. doi: 10.1111/j.1755-3768.2008.01250.x. Epub 2008 Jun 3.
• Results Yamaguchi T. Inflammatory Response in Dry Eye. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES192-DES199. doi: 10.1167/iovs.17-23651.
• Results Luo L, Li DQ, Doshi A, Farley W, Corrales RM, Pflugfelder SC. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4293-301. doi: 10.1167/iovs.03-1145.
• Results Fan NW, Dohlman TH, Foulsham W, McSoley M, Singh RB, Chen Y, Dana R. The role of Th17 immunity in chronic ocular surface disorders. Ocul Surf. 2021 Jan;19:157-168. doi: 10.1016/j.jtos.2020.05.009. Epub 2020 May 26.
• Results Dohlman TH, Chauhan SK, Kodati S, Hua J, Chen Y, Omoto M, Sadrai Z, Dana R. The CCR6/CCL20 axis mediates Th17 cell migration to the ocular surface in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Jun 12;54(6):4081-91. doi: 10.1167/iovs.12-11216.
• Results De Paiva CS, Chotikavanich S, Pangelinan SB, Pitcher JD 3rd, Fang B, Zheng X, Ma P, Farley WJ, Siemasko KF, Niederkorn JY, Stern ME, Li DQ, Pflugfelder SC. IL-17 disrupts corneal barrier following desiccating stress. Mucosal Immunol. 2009 May;2(3):243-53. doi: 10.1038/mi.2009.5. Epub 2009 Feb 25.
• Results Subbarayal B, Chauhan SK, Di Zazzo A, Dana R. IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity. J Immunol. 2016 Nov 1;197(9):3464-3470. doi: 10.4049/jimmunol.1502641. Epub 2016 Sep 21.
• Results Melnikov S, Mayan H, Uchida S, Holtzman EJ, Farfel Z. Cyclosporine metabolic side effects: association with the WNK4 system. Eur J Clin Invest. 2011 Oct;41(10):1113-20. doi: 10.1111/j.1365-2362.2011.02517.x. Epub 2011 Mar 24.
• Results Park B, Lee IS, Hyun SW, Jo K, Lee TG, Kim JS, Kim CS. The Protective Effect of Polygonum cuspidatum (PCE) Aqueous Extract in a Dry Eye Model. Nutrients. 2018 Oct 19;10(10):1550. doi: 10.3390/nu10101550.
• Results Perry HD, Solomon R, Donnenfeld ED, Perry AR, Wittpenn JR, Greenman HE, Savage HE. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthalmol. 2008 Aug;126(8):1046-50. doi: 10.1001/archopht.126.8.1046.
• Results de Paiva CS, Pflugfelder SC, Ng SM, Akpek EK. Topical cyclosporine A therapy for dry eye syndrome. Cochrane Database Syst Rev. 2019 Sep 13;9(9):CD010051. doi: 10.1002/14651858.CD010051.pub2.
• Results Holland EJ, Darvish M, Nichols KK, Jones L, Karpecki PM. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. Ocul Surf. 2019 Jul;17(3):412-423. doi: 10.1016/j.jtos.2019.02.012. Epub 2019 Mar 4.
• Results Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010 Sep;14(9):2190-9. doi: 10.1111/j.1582-4934.2010.01151.x.
• Results Han Y, Yang J, Fang J, Zhou Y, Candi E, Wang J, Hua D, Shao C, Shi Y. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct Target Ther. 2022 Mar 21;7(1):92. doi: 10.1038/s41392-022-00932-0.
• Results Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012 Jan;20(1):14-20. doi: 10.1038/mt.2011.211. Epub 2011 Oct 18.
• Results Yao G, Qi J, Liang J, Shi B, Chen W, Li W, Tang X, Wang D, Lu L, Chen W, Shi S, Hou Y, Sun L. Mesenchymal stem cell transplantation alleviates experimental Sjogren's syndrome through IFN-beta/IL-27 signaling axis. Theranostics. 2019 Oct 21;9(26):8253-8265. doi: 10.7150/thno.37351. eCollection 2019.
• Results Li Y, Ma K, Zhang L, Xu H, Zhang N. Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells Alleviate Dextran Sulfate Sodium-Induced Colitis by Increasing Regulatory T Cells in Mice. Front Cell Dev Biol. 2020 Nov 24;8:604021. doi: 10.3389/fcell.2020.604021. eCollection 2020.
• Results Lee MJ, Ko AY, Ko JH, Lee HJ, Kim MK, Wee WR, Khwarg SI, Oh JY. Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye. Mol Ther. 2015 Jan;23(1):139-46. doi: 10.1038/mt.2014.159. Epub 2014 Aug 25.
• Results Villatoro AJ, Fernandez V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed Res Int. 2015;2015:527926. doi: 10.1155/2015/527926. Epub 2015 Feb 23.
• Results Sgrignoli MR, Silva DA, Nascimento FF, Sgrignoli DAM, Nai GA, da Silva MG, de Barros MA, Bittencourt MKW, de Morais BP, Dinallo HR, Foglia BTD, Cabrera WB, Fares EC, Andrade SF. Reduction in the inflammatory markers CD4, IL-1, IL-6 and TNFalpha in dogs with keratoconjunctivitis sicca treated topically with mesenchymal stem cells. Stem Cell Res. 2019 Aug;39:101525. doi: 10.1016/j.scr.2019.101525. Epub 2019 Jul 31.
• Zhang D, Chen T, Liang Q, Feng X, Jiang J, Chen Z, Tang Y, Chu Y, Wang B, Hu K. A first-in-human, prospective pilot trial of umbilical cord-derived mesenchymal stem cell eye drops therapy for patients with refractory non-Sjogren's and Sjogren's syndrome dry eye disease. Stem Cell Res Ther. 2025 Apr 23;16(1):202. doi: 10.1186/s13287-025-04292-8.

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Indications