Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

References

• Shen Y. Stem cell therapies for retinal diseases: from bench to bedside. J Mol Med. 2020;98(10):1347–1368. doi:10.1007/s00109-020-01960-5
   Web of Science ®Google Scholar
• Eandi CM, Alovisi C, De Sanctis U, Grignolo FM. Treatment for neovascular age related macular degeneration: the state of the art. Eur J Pharmacol. 2016;787:78–83. doi:10.1016/j.ejphar.2016.03.002
   Web of Science ®Google Scholar
• Singh SR, Fung AT, Fraser-Bell S, et al. One-year outcomes of anti-vascular endothelial growth factor therapy in peripapillary choroidal neovascularisation. Br J Ophthalmol. 2020;104(5):678–683. doi:10.1136/bjophthalmol-2019-314542
   Web of Science ®Google Scholar
• Ran X, Cai WJ, Huang XF, et al. ‘RetinoGenetics’: a comprehensive mutation database for genes related to inherited retinal degeneration. Database. 2014;2014:bau071–bau071. doi:10.1093/database/bau047
   Google Scholar
• Prado DA, Acosta-Acero M, Maldonado RS. Gene therapy beyond luxturna: a new horizon of the treatment for inherited retinal disease. Curr Opin Ophthalmol. 2020;31(3):147–154. doi:10.1097/icu.0000000000000660
   PubMed Web of Science ®Google Scholar
• da Cruz L, Dorn JD, Humayun MS, et al. Five-year safety and performance results from the argus II retinal prosthesis system clinical trial. Ophthalmology. 2016;123(10):2248–2254. doi:10.1016/j.ophtha.2016.06.049
   PubMed Web of Science ®Google Scholar
• Krick TW, Bressler NM. Recent clinically relevant highlights from the diabetic retinopathy clinical research network. Curr Opin Ophthalmol. 2018;29(3):199–205. doi:10.1097/icu.0000000000000472
   Web of Science ®Google Scholar
• Petrus-Reurer S, Kumar P, Padrell Sánchez S, et al. Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration. Stem Cells Transl Med. 2020;9(8):936–953. doi:10.1002/sctm.19-0396
   PubMed Web of Science ®Google Scholar
• Mazzilli JL, Snook JD, Simmons K, et al. A preclinical safety study of human embryonic stem cell-derived retinal pigment epithelial cells for macular degeneration. J Ocular Pharmacol Ther. 2020;36(1):65–69. doi:10.1089/jop.2019.0039
   PubMed Web of Science ®Google Scholar
• Wang ST, Chen LL, Zhang P, et al. Transplantation of retinal progenitor cells from optic cup-like structures differentiated from human embryonic stem cells in vitro and in vivo generation of retinal ganglion-like cells. Stem Cells Dev. 2019;28(4):258–267. doi:10.1089/scd.2018.0076
   Web of Science ®Google Scholar
• Wang Z, Gao F, Zhang M, et al. Intravitreal injection of human retinal progenitor cells for treatment of retinal degeneration. Med Sci Monitor. 2020;26:e921184–e921184. doi:10.12659/MSM.921184
   PubMed Web of Science ®Google Scholar
• Aboualizadeh E, Phillips MJ, McGregor JE, et al. Imaging transplanted photoreceptors in living nonhuman primates with single-cell resolution. Stem Cell Rep. 2020;15(2):482–497. doi:10.1016/j.stemcr.2020.06.019
   Web of Science ®Google Scholar
• Tu HY, Watanabe T, Shirai H, et al. Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration. EBioMedicine. 2019;39:562–574. doi:10.1016/j.ebiom.2018.11.028
   PubMed Web of Science ®Google Scholar
• Zhu D, Xie M, Gademann F, et al. Protective effects of human iPS-derived retinal pigmented epithelial cells on retinal degenerative disease. Stem Cell Res Ther. 2020;11(1):98. doi:10.1186/s13287-020-01608-8
   PubMed Web of Science ®Google Scholar
• Surendran H, Nandakumar S, Reddy KV, et al. Transplantation of retinal pigment epithelium and photoreceptors generated concomitantly via small molecule-mediated differentiation rescues visual function in rodent models of retinal degeneration. Stem Cell Res Ther. 2021;12(1):70. doi:10.1186/s13287-021-02134-x
   Web of Science ®Google Scholar
• Salas A, Duarri A, Fontrodona L, et al. Cell therapy with hiPSC-derived RPE cells and RPCs prevents visual function loss in a rat model of retinal degeneration. Mol Ther Methods Clin Develop. 2021;20:688–702. doi:10.1016/j.omtm.2021.02.006
   Web of Science ®Google Scholar
• Collin J, Zerti D, Queen R, et al. CRX expression in pluripotent stem cell-derived photoreceptors marks a transplantable subpopulation of early cones. Stem Cells (Dayton, Ohio). 2019;37(5):609–622. doi:10.1002/stem.2974
   Web of Science ®Google Scholar
• Sharma R, Khristov V, Rising A, et al. Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. Sci Transl Med. 2019;11(475):eaat5580. doi:10.1126/scitranslmed.aat5580
   Web of Science ®Google Scholar
• Cho H, Macklin BL, Lin YY, et al. iPSC-derived endothelial cell response to hypoxia via SDF1a/CXCR4 axis facilitates incorporation to revascularize ischemic retina. JCI Insight. 2020;5(6). doi:10.1172/jci.insight.131828
   Web of Science ®Google Scholar
• Alsaeedi HA, Koh AE, Lam C, et al. Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration. J Photochem Photobiol B. 2019;198:111561. doi:10.1016/j.jphotobiol.2019.111561
   Web of Science ®Google Scholar
• Liu X, Xie J, Yang L, et al. Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions. J Cell Mol Med. 2020;24(6):3346–3358. doi:10.1111/jcmm.15008
   PubMed Web of Science ®Google Scholar
• Yu B, Shao H, Su C, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016;6:34562. doi:10.1038/srep34562
   Web of Science ®Google Scholar
• Manuguerra-Gagné R, Boulos PR, Ammar A, et al. Transplantation of mesenchymal stem cells promotes tissue regeneration in a glaucoma model through laser-induced paracrine factor secretion and progenitor cell recruitment. Stem Cells (Dayton, Ohio). 2013;31(6):1136–1148. doi:10.1002/stem.1364
   PubMed Web of Science ®Google Scholar
• Roubeix C, Godefroy D, Mias C, et al. Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma. Stem Cell Res Ther. 2015;6(1):177. doi:10.1186/s13287-015-0168-0
   PubMed Web of Science ®Google Scholar
• Yu C, Yang K, Meng X, Cao B, Wang F. Downregulation of long noncoding RNA MIAT in the retina of diabetic rats with tail-vein injection of human umbilical-cord mesenchymal stem cells. Int J Med Sci. 2020;17(5):591–598. doi:10.7150/ijms.38078
   Web of Science ®Google Scholar
• Ezquer M, Urzua CA, Montecino S, Leal K, Conget P, Ezquer F. Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Res Ther. 2016;7:42. doi:10.1186/s13287-016-0299-y
   PubMed Web of Science ®Google Scholar
• Mead B, Amaral J, Tomarev S. Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma. Invest Ophthalmol Vis Sci. 2018;59(2):702–714. doi:10.1167/iovs.17-22855
   Web of Science ®Google Scholar
• Rajashekhar G, Ramadan A, Abburi C, et al. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy. PLoS One. 2014;9(1):e84671. doi:10.1371/journal.pone.0084671
   PubMed Web of Science ®Google Scholar
• Elshaer SL, Evans W, Pentecost M, et al. Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2(Akita) mouse. Stem Cell Res Ther. 2018;9(1):322. doi:10.1186/s13287-018-1059-y
   Web of Science ®Google Scholar
• Machalińska A, Kawa M, Pius-Sadowska E, et al. Long-term neuroprotective effects of NT-4-engineered mesenchymal stem cells injected intravitreally in a mouse model of acute retinal injury. Invest Ophthalmol Vis Sci. 2013;54(13):8292–8305. doi:10.1167/iovs.13-12221
   Web of Science ®Google Scholar
• Wang J, Zhang W, He GH, Wu B, Chen S. Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo. Int J Ophthalmol. 2018;11(5):766–772. doi:10.18240/ijo.2018.05.08
   Web of Science ®Google Scholar
• Kim JY, Park S, Park SH, et al. Overexpression of pigment epithelium-derived factor in placenta-derived mesenchymal stem cells promotes mitochondrial biogenesis in retinal cells. Lab Invest. 2021;101(1):51–69. doi:10.1038/s41374-020-0470-z
   Web of Science ®Google Scholar
• Zhang W, Wang Y, Kong J, Dong M, Duan H, Chen S. Therapeutic efficacy of neural stem cells originating from umbilical cord-derived mesenchymal stem cells in diabetic retinopathy. Sci Rep. 2017;7(1):408. doi:10.1038/s41598-017-00298-2
   PubMed Web of Science ®Google Scholar
• Banin E, Barak A, Boyer DS, et al. Phase I/IIa Clinical Trial of Human Embryonic Stem Cell (hESC)-derived retinal pigmented epithelium (RPE, OpRegen) transplantation in advanced dry form Age-Related Macular Degeneration (AMD): interim results. Invest Ophthalmol Vis Sci. 2019;60(9):6402.
   Web of Science ®Google Scholar
• Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label Phase 1/2 studies. Lancet (London, England). 2015;385(9967):509–516. doi:10.1016/s0140-6736(14)61376-3
   PubMed Web of Science ®Google Scholar
• Song WK, Park KM, Kim HJ, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Rep. 2015;4(5):860–872. doi:10.1016/j.stemcr.2015.04.005
   PubMed Web of Science ®Google Scholar
• Riemann CD, Banin E, Barak A, et al. Phase I/IIa clinical trial of Human Embryonic Stem Cell (hESC)-derived Retinal Pigmented Epithelium (RPE, OpRegen) transplantation in advanced dry form Age-Related Macular Degeneration (AMD): interim results. Invest Ophthalmol Vis Sci. 2020;61(7):865.
   Web of Science ®Google Scholar
• da Cruz L, Fynes K, Georgiadis O, et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol. 2018;36(4):328–337. doi:10.1038/nbt.4114
   PubMed Web of Science ®Google Scholar
• Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;376(11):1038–1046. doi:10.1056/NEJMoa1608368
   PubMed Web of Science ®Google Scholar
• Takagi S, Mandai M, Gocho K, et al. Evaluation of transplanted autologous induced pluripotent stem cell-derived retinal pigment epithelium in exudative age-related macular degeneration. Ophthalmol Retina. 2019;3(10):850–859. doi:10.1016/j.oret.2019.04.021
   PubMedGoogle Scholar
• Sung Y, Lee SM, Park M, et al. Treatment of traumatic optic neuropathy using human placenta-derived mesenchymal stem cells in Asian patients. Regen Med. 2020;15(10):2163–2179. doi:10.2217/rme-2020-0044
   Web of Science ®Google Scholar
• Tuekprakhon A, Sangkitporn S, Trinavarat A, et al. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa. Stem Cell Res Ther. 2021;12(1):52. doi:10.1186/s13287-020-02122-7
   Web of Science ®Google Scholar
• Kahraman NS, Oner A. Umbilical cord derived mesenchymal stem cell implantation in retinitis pigmentosa: a 6-month follow-up results of a Phase 3 trial. Int J Ophthalmol. 2020;13(9):1423–1429. doi:10.18240/ijo.2020.09.14
   Web of Science ®Google Scholar
• Zhao T, Liang Q, Meng X, et al. Intravenous infusion of umbilical cord mesenchymal stem cells maintains and partially improves visual function in patients with advanced retinitis pigmentosa. Stem Cells Dev. 2020;29(16):1029–1037. doi:10.1089/scd.2020.0037
   Web of Science ®Google Scholar
• Adak S, Magdalene D, Deshmukh S, Das D, Jaganathan BG. A review on mesenchymal stem cells for treatment of retinal diseases. Stem Cell Rev Rep. 2021;1–20. doi:10.1007/s12015-020-10090-x
   Web of Science ®Google Scholar
• Özmert E, Arslan U. Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results. Stem Cell Res Ther. 2020;11(1):25. doi:10.1186/s13287-020-1549-6
   Web of Science ®Google Scholar
• Gu X, Yu X, Zhao C, et al. Efficacy and safety of autologous bone marrow mesenchymal stem cell transplantation in patients with diabetic retinopathy. Cell Physiol Biochem. 2018;49(1):40–52. doi:10.1159/000492838
   Google Scholar
• Vilela CAP, Messias A, Calado RT, et al. Retinal function after intravitreal injection of autologous bone marrow-derived mesenchymal stromal cells in advanced glaucoma. Doc Ophthalmol. 2021;143(1):33–38. doi:10.1007/s10633-021-09817-z
   Web of Science ®Google Scholar
• Wiącek MP, Gosławski W, Grabowicz A, et al. Long-term effects of adjuvant intravitreal treatment with autologous bone marrow-derived lineage-negative cells in retinitis pigmentosa. Stem Cells Int. 2021;2021:6631921. doi:10.1155/2021/6631921
   Web of Science ®Google Scholar
• Limoli PG, Limoli C, Vingolo EM, Scalinci SZ, Nebbioso M. Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study. Oncotarget. 2016;7(30):46913–46923. doi:10.18632/oncotarget.10442
   Google Scholar
• Limoli PG, Vingolo EM, Morales MU, Nebbioso M, Limoli C. Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration. Medicine. 2014;93(29):e355. doi:10.1097/md.0000000000000355
   Web of Science ®Google Scholar
• 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. Graefe’s Arch Clin Exp Ophthalmol/Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2018;256(11):2041–2052. doi:10.1007/s00417-018-4097-3
   Web of Science ®Google Scholar
• Wen YT, Ho YC, Lee YC, Ding DC, Liu PK, Tsai RK. The benefits and hazards of intravitreal Mesenchymal Stem Cell (MSC) based-therapies in the experimental ischemic optic neuropathy. Int J Mol Sci. 2021;22(4):2117. doi:10.3390/ijms22042117
   Web of Science ®Google Scholar
• Zerti D, Hilgen G, Dorgau B, et al. Transplanted pluripotent stem cell-derived photoreceptor precursors elicit conventional and unusual light responses in mice with advanced retinal degeneration. Stem Cells (Dayton, Ohio). 2021;39(7):882–896. doi:10.1002/stem.3365
   Web of Science ®Google Scholar
• Khine KT, Albini TA, Lee RK. Chronic retinal detachment and neovascular glaucoma after intravitreal stem cell injection for Usher Syndrome. Am J Ophthalmol Case Rep. 2020;18:100647. doi:10.1016/j.ajoc.2020.100647
   Google Scholar
• Rong AJ, Lam BL, Ansari ZA, Albini TA. Vision loss secondary to autologous adipose stem cell injections: a rising problem. JAMA Ophthalmol. 2018;136(1):97–99. doi:10.1001/jamaophthalmol.2017.5453
   Web of Science ®Google Scholar
• Hu C, La H, Wei X, et al. Transplantation site affects the outcomes of adipose-derived stem cell-based therapy for retinal degeneration. Stem Cells Int. 2020;2020:9625798. doi:10.1155/2020/9625798
   PubMed Web of Science ®Google Scholar
• Bartsch U, Oriyakhel W, Kenna PF, et al. Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice. Exp Eye Res. 2008;86(4):691–700. doi:10.1016/j.exer.2008.01.018
   Web of Science ®Google Scholar
• Gasparini SJ, Llonch S, Borsch O, Ader M. Transplantation of photoreceptors into the degenerative retina: current state and future perspectives. Prog Retin Eye Res. 2019;69:1–37. doi:10.1016/j.preteyeres.2018.11.001
   Web of Science ®Google Scholar
• Pan T, Shen H, Yuan S, et al. Combined transplantation with human mesenchymal stem cells improves retinal rescue effect of human fetal RPE cells in retinal degeneration mouse model. Invest Ophthalmol Vis Sci. 2020;61(8):9. doi:10.1167/iovs.61.8.9
   PubMed Web of Science ®Google Scholar
• Huang L, You J, Yao Y, Xie M. Interleukin-13 gene modification enhances grafted mesenchymal stem cells survival after subretinal transplantation. Cell Mol Neurobiol. 2020;40(5):725–735. doi:10.1007/s10571-019-00768-3
   Web of Science ®Google Scholar
• Colombe Dromel P, Singh D, Alexander-Katz A, Kurisawa M, Spector M, Young M. Injectable gelatin hydroxyphenyl propionic acid hydrogel protects human retinal progenitor cells (hRPCs) from shear stress applied during small-bore needle injection. Appl Mater Today. 2020;19:100602. doi:10.1016/j.apmt.2020.100602
   Web of Science ®Google Scholar
• Tian Y, Davis R, Zonca MR Jr, Stern JH, Temple S, Xie Y. Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation. J Tissue Eng Regen Med. 2019;13(1):76–86. doi:10.1002/term.2770
   Web of Science ®Google Scholar
• Costa LA, Eiro N, Fraile M, et al. Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses. Cell Mol Life Sci. 2021;78(2):447–467. doi:10.1007/s00018-020-03600-0
   PubMed Web of Science ®Google Scholar