مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
From Donor Tissue to iPSC-Derived Cells: Future Perspectives of RPE Transplantation in Visual Disorders
From Donor Tissue to iPSC-Derived Cells: Future Perspectives of RPE Transplantation in Visual Disorders
Razieh Heidari,1,*Vahideh Assadolhi,2Somayeh Reiisi,3
1. Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran. 2. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Introduction: The retinal pigment epithelium (RPE) plays a critical role in retinal health, supporting photoreceptors through functions like phagocytosis, nutrient transport, and secretion of growth factors. RPE degeneration is central to many vision-threatening disorders, particularly age-related macular degeneration (AMD). Various RPE transplantation strategies have been explored over the past few decades, ranging from autologous tissue grafts to stem cell-derived RPE therapies. While early attempts using donor tissue faced challenges including immune rejection and limited integration, recent advances in stem cell technology have opened up new possibilities. Embryonic and induced pluripotent stem cell (iPSC)-derived RPE cells have shown promising results in preclinical and clinical trials. Nevertheless, issues such as immune response, proper graft adhesion, and surgical complications remain major hurdles. This review discusses the evolution of RPE transplantation approaches, recent progress with stem cell-based therapies, and the current limitations and future perspectives in the field.
Methods: Early RPE transplantation methods involved surgical removal of abnormal blood vessels in conditions like choroidal neovascularization.followed by the implantation of healthy RPE cells. Techniques included autologous transplantation from the peripheral retina, fetal donor tissue grafts, and cadaveric RPE sheets. These methods often involved invasive surgeries, with limited visual improvements and frequent complications such as proliferative vitreoretinopathy (PVR). In more recent efforts, stem cell-derived RPE cells produced from human embryonic stem cells (ESCs) or iPSCs have been differentiated into RPE-like cells and transplanted as cell suspensions or monolayers. Surgical techniques were developed to deliver these cells subretinally with the goal of restoring function in patients with AMD or inherited retinal dystrophies.
Results: Clinical trials have demonstrated that RPE transplantation is biologically feasible and, in some cases, can yield visual improvement. Fetal donor RPE sheets have shown long-term viability in selected cases despite HLA mismatch, although immune rejection and surgical trauma often led to failure. Autologous transplantation initially appeared promising for avoiding rejection, but long-term outcomes were limited by poor graft integration and functional performance. Furthermore, age-related changes in Bruch’s membrane impaired the adhesion and polarity of transplanted RPE cells. Trials using stem cell-derived RPE cells, particularly from ESCs and iPSCs, reported encouraging safety outcomes and moderate functional improvements. These cells demonstrated typical RPE characteristics and were tolerated by the subretinal environment, though immune reactions and surgical complications like fibrosis and cell reflux were still observed. Newer efforts focus on transplanting RPE as organized monolayers on bioengineered scaffolds to promote proper integration and polarity.
Conclusion: Transplantation of the retinal pigment epithelium remains a promising therapeutic option for retinal degenerative diseases, particularly AMD. While stem cell-derived RPE therapies have overcome some limitations of donor tissue availability and immune compatibility, significant barriers persist. These include immune rejection, challenges in graft attachment and survival, and complications associated with surgical delivery. The future of RPE therapy lies in combining stem cell biology with advancements in tissue engineering, gene editing, and immunomodulation. iPSC-derived, patient-specific RPE grafts and the use of biocompatible scaffolds may offer personalized and more durable treatment options. Continued research and clinical trials are essential to fully realize the potential of RPE transplantation in restoring vision.