The Role of Stem Cells in Diabetic Retinopathy: A Systematic Review (2020–2025)
The Role of Stem Cells in Diabetic Retinopathy: A Systematic Review (2020–2025)
Dr Vaibhav Sharma*1, Dr Saakshi Sarin2
1. Dr Vaibhav Sharma, specialist ophthalmologist, Aster Jubliee Medical Complex, UAE.
2. Dr Saakshi Sarin, Specialist cardiologist, Aster royal clinic , Arabian Ranches , Dubai
*Correspondence to: Vaibhav Sharma, specialist ophthalmologist, Aster Jubliee Medical Complex, UAE.
Copyright
© 2025 Vaibhav Sharma. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 12 May 2025
Published: 01 July 2025
Abstract:
Background: Diabetic retinopathy (DR), a severe microvascular complication of diabetes mellitus, remains a principal cause of blindness globally. Conventional treatments such as
anti-VEGF agents, laser photocoagulation, and vitrectomy are often limited by symptomatic relief without true neurovascular repair.
Objective: To systematically review and evaluate studies conducted from 2020 to 2025 on the therapeutic application of stem cells in DR, focusing on efficacy, safety, mechanisms of action, and translational potential.
Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted for studies published between January 2020 and May 2025. Inclusion criteria encompassed preclinical and clinical studies evaluating stem cell-based therapy in DR models or patients. Data were extracted on study design, cell type, delivery method, outcomes, and adverse effects.
Results: From 1,278 studies initially identified, 48 met inclusion criteria. Mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and endothelial progenitor cells (EPCs) were most commonly studied. Preclinical evidence consistently supports anti-inflammatory, angiogenic modulation, and neuroprotection by stem cells. Early-phase clinical trials show safety, with some reporting improved visual acuity and central macular thickness. Challenges persist in cell delivery, immune compatibility, and long-term integration.
Conclusion: Stem cell therapy offers a regenerative strategy for DR beyond symptom control. Despite encouraging progress, standardized protocols and large-scale trials are needed to validate clinical efficacy.
The Role of Stem Cells in Diabetic Retinopathy: A Systematic Review (2020–2025)
Introduction
Diabetic retinopathy (DR) affects over 100 million individuals globally and is a major cause of visual impairment and blindness in working-age adults. The pathogenesis involves chronic hyperglycemia-induced retinal microvascular dysfunction, leading to capillary occlusion, ischemia, neovascularization, and neurodegeneration. Current treatments, including anti-VEGF therapy, corticosteroids, and surgical interventions, target vascular components without reversing retinal damage.
Stem cell therapy offers promise in regenerating retinal tissue, preserving neuronal function, and restoring the integrity of the retinal vasculature. Stem cells possess self-renewal and differentiation capabilities and can modulate the retinal microenvironment via paracrine signaling. This systematic review aims to comprehensively assess the last five years of evidence regarding the role of stem cells in treating DR.
Methods
Search Strategy: A systematic search of literature databases (PubMed, Scopus, Web of Science, Embase) was conducted using combinations of the keywords: “diabetic retinopathy”, “stem cell therapy”, “mesenchymal stem cells”, “iPSCs”, “EPCs”, “regenerative medicine”. Filters were applied to limit results from January 2020 to May 2025 and to include English-language articles only.
Inclusion Criteria:
- Peer-reviewed clinical trials or preclinical studies
- Use of stem cell-based intervention in DR
- Outcome measures including retinal repair, angiogenesis, visual acuity, or molecular markers
Exclusion Criteria:
- Editorials, commentaries, or conference abstracts
- Studies not directly evaluating DR
- In vitro studies without in vivo validation
Data Extraction and Analysis: Two reviewers independently extracted data on study design, stem cell type, delivery method, outcomes, and adverse events. Risk of bias was assessed using the SYRCLE tool for preclinical studies and Cochrane Risk of Bias tool for clinical trials.
Results
48 studies were included: 28 preclinical, 12 clinical, 8 reviews. Most commonly used stem cells: MSCs, iPSCs, and EPCs. Delivery methods included intravitreal, subretinal, and systemic injections. Clinical trials demonstrated safety and moderate improvements in visual function.
Summary Table of Clinical Trials:
|
Study |
Cell Type |
Phase |
Patients |
Outcome |
|
NCT03420851 |
UC-MS C |
Phase I |
30 |
Improved BCVA, reduced retinal edema |
|
NCT03784519 |
BM-MS C |
Phase II |
40 |
Safe, modest functional improvement |
|
Takahashi et al. (2023, Japan) |
iPSC-RP E |
Phase I |
5 |
Functional integration, no tumor formation |
Discussion
Stem cell-based therapies for DR offer a multifaceted approach—addressing not only vascular leakage but also neuronal apoptosis and inflammation. The immunomodulatory effect of MSCs has been the most consistently reported benefit. iPSC-based approaches show extraordinary promise for retinal cell replacement but are hindered by safety and cost barriers.
Standardization of stem cell sourcing, expansion, and delivery is a major limitation across trials. Ethical and regulatory hurdles persist. There is also a need for harmonized outcome measures and advanced imaging tools.
Conclusion
Stem cell therapy has emerged as a compelling therapeutic avenue for diabetic retinopathy. While preclinical data strongly support regenerative and anti-inflammatory effects, clinical translation is still in early stages. Focused clinical trials with larger cohorts, long-term follow-up, and standardized protocols are essential for realizing the full therapeutic potential of stem cells in DR.
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