Stem Cell Therapy in Nonneovascular Age-Related Macular Degeneration

Kashani, Amir H

doi:10.1167/iovs.15-17681

Cited by 17 publications

(16 citation statements)

References 107 publications

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“…Human embryonic stem cell-derived RPE (hESC-RPE) represents an ideal source of tissue for treatment of retinal degenerations (8) and advanced NNAMD (4,9). Multiple protocols have been developed for the derivation of RPE from pluripotent stem cells (10).…”

Section: Introductionmentioning

confidence: 99%

A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration

Lebkowski²,

et al. 2018

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Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of non-neovascular age-related macular degeneration (NNAMD). Without the RPE, a majority of overlying photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement strategies may delay disease progression or restore vision. A prospective, interventional, U.S. Food and Drug Administration-cleared, phase 1/2a study is being conducted to assess the safety and efficacy of a composite subretinal implant in subjects with advanced NNAMD. The composite implant, termed the California Project to Cure Blindness-Retinal Pigment Epithelium 1 (CPCB-RPE1), consists of a polarized monolayer of human embryonic stem cell-derived RPE (hESC-RPE) on an ultrathin, synthetic parylene substrate designed to mimic Bruch's membrane. We report an interim analysis of the phase 1 cohort consisting of five subjects. Four of five subjects enrolled in the study successfully received the composite implant. In all implanted subjects, optical coherence tomography imaging showed changes consistent with hESC-RPE and host photoreceptor integration. None of the implanted eyes showed progression of vision loss, one eye improved by 17 letters and two eyes demonstrated improved fixation. The concurrent structural and functional findings suggest that CPCB-RPE1 may improve visual function, at least in the short term, in some patients with severe vision loss from advanced NNAMD.

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Section: Introductionmentioning

confidence: 99%

A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration

Lebkowski²,

et al. 2018

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“…There are two types of AMD: neovascular (wet) and non-neovascular (dry). Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD remains untreatable [1, 2]. Replacement of the diseased RPE cells with healthy transplanted RPE cells is a feasible approach for a new AMD therapy [3, 4].…”

Section: Introductionmentioning

confidence: 99%

The formation of a functional retinal pigment epithelium occurs on porous polytetrafluoroethylene substrates independently of the surface chemistry

Kearns

Tasker

Zhuola

et al. 2017

J Mater Sci: Mater Med

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Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells may have the potential to preserve or restore vision in patients affected by blinding diseases such as age-related macular degeneration (AMD). One of the critical steps in achieving this is the ability to grow a functioning retinal pigment epithelium, which may need a substrate on which to grow and to aid transplantation. Tailoring the physical and chemical properties of the substrate should help the engineered tissue to function in the long term. The purpose of the study was to determine whether a functioning monolayer of RPE cells could be produced on expanded polytetrafluoroethylene substrates modified by either an ammonia plasma treatment or an n-Heptylamine coating, and whether the difference in surface chemistries altered the extracellular matrix the cells produced. Primary human RPE cells were able to form a functional, cobblestone monolayer on both substrates, but the formation of an extracellular matrix to exhibit a network structure took months, whereas on non-porous substrates with the same surface chemistry, a similar appearance was observed after a few weeks. This study suggests that the surface chemistry of these materials may not be the most critical factor in the development of growth of a functional monolayer of RPE cells as long as the cells can attach and proliferate on the surface. This has important implications in the design of strategies to optimise the clinical outcomes of subretinal transplant procedures.Graphical Abstract

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“…3 With the advancement of stem cell technology and regenerative medicine, RPE cell replacement therapy has been considered as a promising therapeutic for these diseases, and several clinical trials in AMD/RP patients are underway worldwide. [4][5][6][7][8] Therefore, establishing methods for producing large amounts of RPE seed cells with high quality and at a low cost would be key to bringing stem cell therapy into effect.…”

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confidence: 99%

Self-Formation of RPE Spheroids Facilitates Enrichment and Expansion of hiPSC-Derived RPE Generated on Retinal Organoid Induction Platform

Liu

Xie

Song

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinal pigment epithelium (RPE) and neural retina could be generated concurrently through retinal organoid induction approaches using human induced pluripotent stem cells (hiPSCs), providing valuable sources for cell therapy of retinal degenerations. This study aims to enrich and expand hiPSC-RPE acquired with this platform and explore characteristics of serially passaged RPE cells. METHODS. RPE has been differentiated from hiPSCs with a published retinal organoid induction method. After detachment of neural retina on the 4th week, the remaining mixture was scraped from the dish and subjected to suspension culture for the formation of RPE spheroids. RPE sheets were isolated and digested for expansion. The cellular, molecular, and functional features of expanded RPE cells were evaluated by different assays. RESULTS. Under suspension culture, hiPSC-RPE spheroids with pigmentation self-formed were readily enriched by removing the non-retinal tissues. RPE sheets were further dissected and purified from the spheroids. The individualized RPE cells could be passaged every week for at least 5 times in serum medium, yielding large numbers of cells with high quality in a short period. In addition, when switched to a serum-free medium, the passaged RPE cells could mature in cellular, molecular, and physiological levels, including repigmentation, markers expression, and phagocytosis. CONCLUSIONS. We developed a simple and novel RPE spheroids formation approach to enrich and expand hiPSC-RPE cells generated along with retinal neurons on a universal retinal organoid induction platform. This achievement will reduce the cost and time in producing retinal cells for basic and translational researches, in particular for retinal cell therapy.

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Stem Cell Therapy in Nonneovascular Age-Related Macular Degeneration

Cited by 17 publications

References 107 publications

A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration

A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration

The formation of a functional retinal pigment epithelium occurs on porous polytetrafluoroethylene substrates independently of the surface chemistry

Self-Formation of RPE Spheroids Facilitates Enrichment and Expansion of hiPSC-Derived RPE Generated on Retinal Organoid Induction Platform

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