Keywords:
Stem cell therapy
Ocular disorders
Age-related macular degeneration (AMD)
Induced pluripotent stem cells (iPSCs)
Retinitis pigmentosa
Regenerative medicine

  • Abstract

    Ocular disorders, such as age-related macular degeneration (AMD), glaucoma, and retinitis pigmentosa, are leading causes of vision loss worldwide, with limited treatment options that often focus on slowing disease progression rather than restoring lost vision. Stem cell therapy has emerged as a promising approach to address these challenges by offering the potential to regenerate damaged ocular tissues and restore visual function. This review provides a comprehensive overview of the current advances in stem cell therapy for ocular disorders, discussing the various types of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells, and their specific applications in treating major eye diseases. The review also addresses the technical, ethical, and safety challenges associated with the clinical translation of stem cell-based therapies. Furthermore, it explores emerging technologies such as 3D bioprinting, gene editing, and the development of retinal organoids, which are poised to enhance the efficacy and precision of stem cell therapies in ophthalmology. By analyzing the current state of research and highlighting future directions, this review aims to provide valuable insights into the potential of stem cell therapy to revolutionize the treatment of ocular disorders, offering hope for patients who suffer from debilitating vision loss.

  • References

    1. Vision impairment and blindness. Accessed: September 7, 2024. https://www.who.int/news-room/fact-sheets/detail/blindness-and-visual-impairment.
    2. Ruia S, Kaufman EJ: Macular Degeneration. In: StatPearls. StatPearls Publishing: Treasure Island (FL); 2024.
    3. Dietze J, Blair K, Zeppieri M, Havens SJ: Glaucoma. In: StatPearls. StatPearls Publishing: Treasure Island (FL); 2024.
    4. Wareham LK, Liddelow SA, Temple S, et al.: Solving neurodegeneration: common mechanisms and strategies for new treatments. Mol Neurodegener. 2022, 17:23. 10.1186/s13024-022-00524-0
    5. Niu Y, Ji J, Yao K, Fu Q: Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges. Adv Ophthalmol Pract Res. 2024, 4:52–64. 10.1016/j.aopr.2024.02.001
    6. Coco-Martin RM, Pastor-Idoate S, Pastor JC: Cell Replacement Therapy for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges. Pharmaceutics. 2021, 13:865. 10.3390/pharmaceutics13060865
    7. Nicoară SD, Brie I, Jurj A, Sorițău O: The Future of Stem Cells and Their Derivates in treating Glaucoma. A Critical Point of View. Int J Mol Sci. 2021, 22:11077. 10.3390/ijms222011077
    8. Tomczak W, Winkler-Lach W, Tomczyk-Socha M, Misiuk-Hojło M: Advancements in Ocular Regenerative Therapies. Biology (Basel). 2023, 12:737. 10.3390/biology12050737
    9. Chehelgerdi M, Behdarvand Dehkordi F, Chehelgerdi M, et al.: Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy. Mol Cancer. 2023, 22:189. 10.1186/s12943-023-01873-0
    10. Al Abbar A, Ngai SC, Nograles N, Alhaji SY, Abdullah S: Induced Pluripotent Stem Cells: Reprogramming Platforms and Applications in Cell Replacement Therapy. Biores Open Access. 2020, 9:121–36. 10.1089/biores.2019.0046
    11. Ullah I, Subbarao RB, Rho GJ: Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015, 35:e00191. 10.1042/BSR20150025
    12. Bhatia B, Singhal S, Jayaram H, Khaw PT, Limb GA: Adult Retinal Stem Cells Revisited. Open Ophthalmol J. 2010, 4:30–8. 10.2174/1874364101004010030
    13. Radu M, Brănișteanu DC, Pirvulescu RA, Dumitrescu OM, Ionescu MA, Zemba M: Exploring Stem-Cell-Based Therapies for Retinal Regeneration. Life (Basel). 2024, 14:668. 10.3390/life14060668
    14. Soleimani M, Masoumi A, Momenaei B, et al.: Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery. Expert Opin Biol Ther. 2023, 23:509–25. 10.1080/14712598.2023.2175605
    15. Sasamoto Y, Ksander BR, Frank MH, Frank NY: Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies. Expert Opin Biol Ther. 2018, 18:505–13. 10.1080/14712598.2018.1443442
    16. Voisin A, Pénaguin A, Gaillard A, Leveziel N: Stem cell therapy in retinal diseases. Neural Regen Res. 2022, 18:1478–85. 10.4103/1673-5374.361537
    17. Do JL, Allahwerdy S, David RCC, Weinreb RN, Tuszynski MH, Welsbie DS: Optic Nerve Engraftment of Neural Stem Cells. Invest Ophthalmol Vis Sci. 2021, 62:30. 10.1167/iovs.62.9.30
    18. Calonge M, Nieto-Miguel T, de la Mata A, Galindo S, Herreras JM, López-Paniagua M: Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency. Pharmaceutics. 2021, 13:1483. 10.3390/pharmaceutics13091483
    19. Antonio-Aguirre B, Arevalo JF: Are we there yet to treat patients with geographic atrophy? Int J Retina Vitreous. 2023, 9:72. 10.1186/s40942-023-00493-6
    20. Qi X-Y, Mi C-H, Cao D-R, Chen X-Q, Zhang P: Retinitis pigmentosa and stem cell therapy. Int J Ophthalmol. 2024, 17:1363–9. 10.18240/ijo.2024.07.22
    21. Hu B-Y, Xin M, Chen M, Yu P, Zeng L-Z: Mesenchymal stem cells for repairing glaucomatous optic nerve. Int J Ophthalmol. 2024, 17:748–60. 10.18240/ijo.2024.04.20
    22. Sacchetti M, Rama P, Bruscolini A, Lambiase A: Limbal Stem Cell Transplantation: Clinical Results, Limits, and Perspectives. Stem Cells Int. 2018, 2018:8086269. 10.1155/2018/8086269
    23. Li X-J, Li C-Y, Bai D, Leng Y: Insights into stem cell therapy for diabetic retinopathy: a bibliometric and visual analysis. Neural Regen Res. 2020, 16:172–8. 10.4103/1673-5374.286974
    24. Sharma R, Bose D, Maminishkis A, Bharti K: RETINAL PIGMENT EPITHELIUM REPLACEMENT THERAPY FOR AGE-RELATED MACULAR DEGENERATION – ARE WE THERE YET? Annu Rev Pharmacol Toxicol. 2020, 60:553–72. 10.1146/annurev-pharmtox-010919-023245
    25. Surendran H, Nandakumar S, Reddy K VB, 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, 12:70. 10.1186/s13287-021-02134-x
    26. Fernandes‐Cunha GM, Na K, Putra I, et al.: Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier. Stem Cells Transl Med. 2019, 8:478–89. 10.1002/sctm.18-0178
    27. Yazdanyar A, Zhang P, Dolf C, et al.: Effects of Intravitreal Injection of Human CD34+ Bone Marrow Stem Cells in a Murine Model of Diabetic Retinopathy. Exp Eye Res. 2020, 190:107865. 10.1016/j.exer.2019.107865
    28. Bonnet C, González S, Deng SX: Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives. Stem Cells Transl Med. 2023, 12:714–9. 10.1093/stcltm/szad058
    29. 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, 17:1154–73. 10.1007/s12015-020-10090-x
    30. Oh JY, Lee RH: Mesenchymal stromal cells for treating ocular autoimmune diseases. Prog Retin Eye Res. 2021, 85:100967. 10.1016/j.preteyeres.2021.100967
    31. Volarevic V, Markovic BS, Gazdic M, et al.: Ethical and Safety Issues of Stem Cell-Based Therapy. Int J Med Sci. 2018, 15:36–45. 10.7150/ijms.21666
    32. George B: Regulations and guidelines governing stem cell based products: Clinical considerations. Perspect Clin Res. 2011, 2:94–9. 10.4103/2229-3485.83228
    33. Zhao C, Wang Q, Temple S: Stem cell therapies for retinal diseases: recapitulating development to replace degenerated cells. Development. 2017, 144:1368–81. 10.1242/dev.133108
    34. Liu X, Li W, Fu X, Xu Y: The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives. Front Immunol. 2017, 8:645. 10.3389/fimmu.2017.00645
    35. Li SC, Zhong JF: Twisting immune responses for allogeneic stem cell therapy. World J Stem Cells. 2009, 1:30–5. 10.4252/wjsc.v1.i1.30
    36. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC: Tumorigenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies. Nat Med. 2013, 19:998–1004. 10.1038/nm.3267
    37. Kharbikar BN, Mohindra P, Desai TA: Biomaterials to enhance stem cell transplantation. Cell Stem Cell. 2022, 29:692–721. 10.1016/j.stem.2022.04.002
    38. Pacheco-Herrero M, Soto-Rojas LO, Reyes-Sabater H, Garcés-Ramirez L, de la Cruz López F, Villanueva-Fierro I, Luna-Muñoz J: Current Status and Challenges of Stem Cell Treatment for Alzheimer’s Disease. J Alzheimers Dis. 84:917–35. 10.3233/JAD-200863
    39. Lo B, Parham L: Ethical Issues in Stem Cell Research. Endocr Rev. 2009, 30:204–13. 10.1210/er.2008-0031
    40. Driscoll D, Farnia S, Kefalas P, Maziarz RT: Concise Review: The High Cost of High Tech Medicine: Planning for Market Access. Stem Cells Transl Med. 2017, 6:1723–9. 10.1002/sctm.16-0487
    41. Lappin T, Cheng T: An urgent need for standardization of stem cells and stem cell‐derived products toward clinical applications. Stem Cells Transl Med. 2021, 10:S1–3. 10.1002/sctm.21-0269
    42. Rao Z, Lin Z, Song P, Quan D, Bai Y: Biomaterial-Based Schwann Cell Transplantation and Schwann Cell-Derived Biomaterials for Nerve Regeneration. Front Cell Neurosci. 2022, 16:926222. 10.3389/fncel.2022.926222
    43. Fenton OS, Paolini M, Andresen JL, Müller FJ, Langer R: Outlooks on Three-Dimensional Printing for Ocular Biomaterials Research. J Ocul Pharmacol Ther. 2020, 36:7–17. 10.1089/jop.2018.0142
    44. Fague L, Liu YA, Marsh-Armstrong N: The basic science of optic nerve regeneration. Ann Transl Med. 2021, 9:1276. 10.21037/atm-20-5351
    45. Öner A: Stem Cell Treatment in Retinal Diseases: Recent Developments. Turk J Ophthalmol. 2018, 48:33–8. 10.4274/tjo.89972
    46. Bains KK, Fukuoka H, Hammond GM, Sotozono C, Quantock AJ: Recovering vision in corneal epithelial stem cell deficient eyes. Cont Lens Anterior Eye. 2019, 42:350–8. 10.1016/j.clae.2019.04.006
    47. Sotiropulos K, Kourkoutas D, Almaliotis D, Ploumidou K, Karampatakis V: Ocular stem cells: a narrative review of current clinical trials. Int J Ophthalmol. 2022, 15:1529–37. 10.18240/ijo.2022.09.17
    48. Mirshafiei M, Rashedi H, Yazdian F, Rahdar A, Baino F: Advancements in tissue and organ 3D bioprinting: Current techniques, applications, and future perspectives. Materials & Design. 2024, 240:112853. 10.1016/j.matdes.2024.112853
    49. Tasciotti E, Cabrera FJ, Evangelopoulos M, et al.: The emerging role of nanotechnology in cell and organ transplantation. Transplantation. 2016, 100:1629–38. 10.1097/TP.0000000000001100
    50. Zayed MA, Sultan S, Alsaab HO, et al.: Stem-Cell-Based Therapy: The Celestial Weapon against Neurological Disorders. Cells. 2022, 11:3476. 10.3390/cells11213476
    51. Cuzick J: The importance of long-term participant follow-up in clinical trials. Br J Cancer. 2023, 128:432–8. 10.1038/s41416-022-02038-4
    52. Thompson DA, Iannaccone A, Ali RR, et al.: Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium. Transl Vis Sci Technol. 2020, 9:2. 10.1167/tvst.9.7.2
    53. Burningham S, Ollenberger A, Caulfield T: Commercialization and Stem Cell Research: A Review of Emerging Issues. Stem Cells Dev. 2013, 22:80–4. 10.1089/scd.2013.0317
    54. Paik DT, Chandy M, Wu JC: Patient and Disease–Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics. Pharmacol Rev. 2020, 72:320–42. 10.1124/pr.116.013003
    55. Abdelnour SA, Xie L, Hassanin AA, Zuo E, Lu Y: The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Inherited Diseases. Front Cell Dev Biol. 2021, 9:699597. 10.3389/fcell.2021.699597
    56. Krishani M, Shin WY, Suhaimi H, Sambudi NS: Development of Scaffolds from Bio-Based Natural Materials for Tissue Regeneration Applications: A Review. Gels. 2023, 9:100. 10.3390/gels9020100
    57. Kruczek K, Swaroop A: Pluripotent stem cell‐derived retinal organoids for disease modeling and development of therapies. Stem Cells. 2020, 38:1206–15. 10.1002/stem.3239
    58. Abdulmalek OAAY, Husain KH, AlKhalifa HKAA, Alturani MMAB, Butler AE, Moin ASM: Therapeutic Applications of Stem Cell-Derived Exosomes. Int J Mol Sci. 2024, 25:3562. 10.3390/ijms25063562
    59. Liu K-P, Ma W, Li C-Y, Li L-Y: Neurotrophic factors combined with stem cells in treating sciatic nerve injury in rats: a meta-analysis. Biosci Rep. 2022, 42:BSR20211399. 10.1042/BSR20211399
    60. Wu KY, Mina M, Sahyoun J-Y, Kalevar A, Tran SD: Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration. Sensors (Basel). 2023, 23:5782. 10.3390/s23135782
    61. Harris DT: Stem Cell Banking for Regenerative and Personalized Medicine. Biomedicines. 2014, 2:50–79. 10.3390/biomedicines2010050
    62. Vo QD, Saito Y, Ida T, Nakamura K, Yuasa S: The use of artificial intelligence in induced pluripotent stem cell-based technology over 10-year period: A systematic scoping review. PLoS One. 2024, 19:e0302537. 10.1371/journal.pone.0302537
    63. Wareham LK, Risner ML, Calkins DJ: Protect, Repair, and Regenerate: Towards Restoring Vision in Glaucoma. Curr Ophthalmol Rep. 2020, 8:301–10. 10.1007/s40135-020-00259-5
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to cite

Javed, Z., & Daigavane, S. (2025). Stem Cell Therapy in Ophthalmology: Current Advances and Future Directions for Ocular Disorders- A comprehensive review. Multidisciplinary Reviews, (| Accepted Articles). Retrieved from https://malque.pub/ojs/index.php/mr/article/view/7362
  • Article viewed - 960