Surgical Method for Implantation of a Biosynthetic Retinal Pigment Epithelium Monolayer for Geographic Atrophy: Experience from a Phase 1/2a Study

Kashani, Amir H; Uang, Jeremy; Mert, Melissa; Rahhal, Firas M.; Chan, Clement K.; Avery, Robert L.; Dugel, Pravin U.; Chen, Sanford; Lebkowski, Jane; Clegg, Dennis O.; Hinton, David R.; Humayun, Mark S.

doi:10.1016/j.oret.2019.09.017

Cited by 59 publications

(63 citation statements)

References 34 publications

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“…Host RPE denudation and subretinal transplant of RPE cannot be performed in two separate surgeries, as extensive subretinal fibrosis would prevent subsequent raising of the subretinal blebs required for RPE transplantation. Similar observations are available from a clinical trial with hESC-RPE monolayer grafts in AMD (GA) (Kashani et al, 2020). Future studies will attempt to study rescue in a laser-induced dystrophic RPE model with diseased Bruch's membrane (Sharma et al, 2019) to gauge a possible therapeutic benefit.…”

Section: Discussionmentioning

confidence: 79%

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

et al. 2021

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Summary Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

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Section: Discussionmentioning

confidence: 79%

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

et al. 2021

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“…Thus, Kashani et al have designed an implant using a scaffold, termed the California Project to Cure Blindness-Retinal Pigment Epithelium 1 (CPCB-RPE1), which consists of a polarized monolayer of hESC-derived RPE cells on an ultrathin synthetic parylene (plastic) substrate designed to mimic Bruch's membrane. This group has published data on a cohort of 16 patients with advanced dry AMD (NCT02590692), which demonstrate the technique's safety and suggest that it may improve visual function, since none of the implanted eyes showed the progression of vision loss, one eye improved by 17 letters and two eyes demonstrated improved fixation [59]. The group led by da Cruz et al is investigating a similar RPE patch in severe exudative AMD as a part of The London Project to Cure Blindness (NCT03102138).…”

Section: Rpe Replacementmentioning

confidence: 99%

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

2021

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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.

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“…Parylene-C is a class VI biocompatible polymer having several biomedical applications including the fabrication of Argus ® II Retinal Prosthesis System [100]. Our preclinical and translational studies showed that composite implant of RPE and parylene is a feasible option to rescue visual function [9,[101][102][103]. The parylene material used was semipermeable to molecules of a certain molecular weight when its thickness was reduced to a sub-micron range.…”

Section: Synthetic Biomaterials Used As Scaffoldsmentioning

confidence: 99%

Tissue Engineering Strategies for Retinal Regeneration

Ds¹,

Seiler²,

Patel³

et al. 2021

Preprint

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The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

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Surgical Method for Implantation of a Biosynthetic Retinal Pigment Epithelium Monolayer for Geographic Atrophy: Experience from a Phase 1/2a Study

Cited by 59 publications

References 34 publications

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

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

Tissue Engineering Strategies for Retinal Regeneration

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