Cell Replacement Therapy for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges

Abstract

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Subretinal Injection Techniques for Retinal Disease: A Review

“…Some of the most frequent types of retinal degeneration, such as AMD and IRDs (which include retinitis pigmentosa and Stargardt disease), are caused by the irreversible loss of these cells. Therefore, replacement of damaged tissue using cell therapy could be an interesting option [ 28 , 36 ]. Furthermore, in many cases, cell therapy could be a good treatment as it can be used in both genetic and acquired diseases where the irreversible cell loss would make gene therapy ineffective [ 37 ].…”

Effect of Electrical Stimulation on Ocular Cells: A Means for Improving Ocular Tissue Engineering and Treatments of Eye Diseases

“…Embryonic stem cells have benefited Stargardt's macular dystrophy and dry age-related macular and retinitis pigmentosa patients [ 5 ]. Optic nerve damaged due to trauma, glaucoma, demyelinating optic neuropathy or toxic optic neuropathy, retinitis pigmentosa (RP), age-related macular degeneration (AMD), and retinal vascular accident-related diseases are the most common retinal diseases that are expected to profit from beneficial effects of stem cell therapy in the near future [ 6 ]. Corneal epithelial progenitor cell therapy has also demonstrated a promising approach for corneal regeneration in limbal stem cell deficiency (LSCD) [ 7 ].…”

Advanced Therapy Medicinal Products for Eye Diseases: Goals and Challenges

“…Cell-based therapy for eye diseases is one of the most successful examples of current regenerative medicine. Two excellent review papers deal with this aspect of ATMPs, one of them focused on cell therapy for diseases leading to corneal blindness [2] and the other one on cell replacement for retinal or optic nerve degeneration [3]. Calonge M. et al [2] present the goals and challenges of stem cell-based therapy to treat corneal blindness caused by limbal stem cell deficiency, which affects the stem cell niche located at the corneal limbus.…”

“…This review paper revises the challenges related to the development of cell-based products for the anterior part of the eye and the importance of the close interaction between basic and clinical scientists to succeed. On the other hand, Coco-Martin R. et al [3] focus their review in the posterior part of the eye, specifically in the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases. The authors describe the available cell sources and the challenges involved in the development of such treatments.…”