The Effect of Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa

Summary

This clinical trial aims to study the efficacy of umbilical cord-derived mesenchymal stem cells and their exosomes in the treatment of retinitis pigmentosa. The participants will be randomized into 3 groups. Functional and structural parameters will be compared before and after the injections and also will be compared among the groups to reveal whether stem cell and their exosomes are more effective than placebo.

Timeline

Start

2022-08-05

Primary completion

2023-07-01

Completion

2023-12-15

Publications

• Background Limoli PG, Limoli CSS, Morales MU, Vingolo EM. Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects. Restor Neurol Neurosci. 2020;38(3):223-237. doi: 10.3233/RNN-190970.
• Background Bhattacharya S, Gangaraju R, Chaum E. Recent Advances in Retinal Stem Cell Therapy. Curr Mol Biol Rep. 2017 Sep;3(3):172-182. doi: 10.1007/s40610-017-0069-3. Epub 2017 Jul 10.
• Background Limoli PG, Vingolo EM, Limoli C, Nebbioso M. Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review. Biomedicines. 2019 Nov 30;7(4):94. doi: 10.3390/biomedicines7040094.
• Background Borkowska-Kuczkowska A, Slugocka D, Swiatkowska-Flis B, Boruczkowski D. The use of mesenchymal stem cells for the treatment of progressive retinal diseases: a review. Regen Med. 2019 May;14(4):321-329. doi: 10.2217/rme-2019-0022. Epub 2019 Apr 12.
• Background Jin ZB, Gao ML, Deng WL, Wu KC, Sugita S, Mandai M, Takahashi M. Stemming retinal regeneration with pluripotent stem cells. Prog Retin Eye Res. 2019 Mar;69:38-56. doi: 10.1016/j.preteyeres.2018.11.003. Epub 2018 Nov 9.
• Background Ozmert E, Arslan U. Management of retinitis pigmentosa by Wharton's jelly derived mesenchymal stem cells: preliminary clinical results. Stem Cell Res Ther. 2020 Jan 13;11(1):25. doi: 10.1186/s13287-020-1549-6.
• Background Oner A. Stem Cell Treatment in Retinal Diseases: Recent Developments. Turk J Ophthalmol. 2018 Feb;48(1):33-38. doi: 10.4274/tjo.89972. Epub 2018 Feb 23.
• Background Cotrim CC, Jorge R, Oliveira MC, Pieroni F, Messias AMV, Siqueira RC. Clinical studies using stem cells for treatment of retinal diseases: state of the art. Arq Bras Oftalmol. 2020 Mar-Apr;83(2):160-167. doi: 10.5935/0004-2749.20200037.
• Background Huo DM, Dong FT, Yu WH, Gao F. Differentiation of mesenchymal stem cell in the microenviroment of retinitis pigmentosa. Int J Ophthalmol. 2010;3(3):216-9. doi: 10.3980/j.issn.2222-3959.2010.03.08. Epub 2010 Sep 18.
• Background Satarian L, Nourinia R, Safi S, Kanavi MR, Jarughi N, Daftarian N, Arab L, Aghdami N, Ahmadieh H, Baharvand H. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study. J Ophthalmic Vis Res. 2017 Jan-Mar;12(1):58-64. doi: 10.4103/2008-322X.200164.
• Background Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE 2nd, Parrott MB, Rosenfeld PJ, Flynn HW Jr, Goldberg JL. Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD. N Engl J Med. 2017 Mar 16;376(11):1047-1053. doi: 10.1056/NEJMoa1609583.
• Background Harrell CR, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome. Cells. 2019 May 16;8(5):467. doi: 10.3390/cells8050467.
• Background Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res. 2017 Jul;59:158-177. doi: 10.1016/j.preteyeres.2017.04.004. Epub 2017 Apr 29.
• Background Harrell CR, Simovic Markovic B, Fellabaum C, Arsenijevic A, Djonov V, Arsenijevic N, Volarevic V. Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases. Adv Exp Med Biol. 2018;1089:47-57. doi: 10.1007/5584_2018_219.
• Background Mead B, Tomarev S. Extracellular vesicle therapy for retinal diseases. Prog Retin Eye Res. 2020 Nov;79:100849. doi: 10.1016/j.preteyeres.2020.100849. Epub 2020 Mar 10.
• Background Yaghoubi Y, Movassaghpour A, Zamani M, Talebi M, Mehdizadeh A, Yousefi M. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci. 2019 Sep 15;233:116733. doi: 10.1016/j.lfs.2019.116733. Epub 2019 Aug 5.
• Background Zhang X, Liu J, Yu B, Ma F, Ren X, Li X. Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes. Graefes Arch Clin Exp Ophthalmol. 2018 Nov;256(11):2041-2052. doi: 10.1007/s00417-018-4097-3. Epub 2018 Aug 30.
• Background Ma M, Li B, Zhang M, Zhou L, Yang F, Ma F, Shao H, Li Q, Li X, Zhang X. Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment. Exp Eye Res. 2020 Feb;191:107899. doi: 10.1016/j.exer.2019.107899. Epub 2019 Dec 19.
• Background Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, Zhang Y, Li Q, Zhang X, Li X. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016 Sep 30;6:34562. doi: 10.1038/srep34562.
• Background Zhang W, Wang Y, Kong Y. Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1. Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):294-303. doi: 10.1167/iovs.18-25617.
• Background Hajrasouliha AR, Jiang G, Lu Q, Lu H, Kaplan HJ, Zhang HG, Shao H. Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization. J Biol Chem. 2013 Sep 27;288(39):28058-67. doi: 10.1074/jbc.M113.470765. Epub 2013 Aug 7.
• Background Ha DH, Kim SD, Lee J, Kwon HH, Park GH, Yang SH, Jung JY, Lee JH, Park SR, Youn J, Lee SH, Kim JE, Lim J, Lee HK, Cho BS, Yi YW. Toxicological evaluation of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells. Regul Toxicol Pharmacol. 2020 Aug;115:104686. doi: 10.1016/j.yrtph.2020.104686. Epub 2020 May 22.
• Background Pan D, Chang X, Xu M, Zhang M, Zhang S, Wang Y, Luo X, Xu J, Yang X, Sun X. UMSC-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush. J Chem Neuroanat. 2019 Mar;96:134-139. doi: 10.1016/j.jchemneu.2019.01.006. Epub 2019 Jan 10.
• Background Zhao T, Liang Q, Meng X, Duan P, Wang F, Li S, Liu Y, Yin ZQ. Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells Maintains and Partially Improves Visual Function in Patients with Advanced Retinitis Pigmentosa. Stem Cells Dev. 2020 Aug;29(16):1029-1037. doi: 10.1089/scd.2020.0037. Epub 2020 Jul 15.

Drugs

Indications