Elucidating the phenomenon of HESC-derived RPE: Anatomy of cell genesis, expansion and retinal transplantation

Vugler, Anthony; Carr, Amanda-Jayne F.; Lawrence, Jean M.; Chen, Li Li; Burrell, Kelly; Wright, Andrew; Lundh, Peter; Semo, Ma’ayan; Ahmado, Ahmad; Gias, Carlos; Cruz, Lyndon da; Moore, H. D. M.; Andrews, Peter W.; Walsh, James; Coffey, Peter

doi:10.1016/j.expneurol.2008.09.007

Cited by 248 publications

(260 citation statements)

References 66 publications

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“…Two proteins were studied: the tight junction protein ZO-1 and the chaperone RPE-specific protein 65 kDa (RPE65), which is involved in the visual cycle of retinal. These are two of the most common RPE markers used to evaluate the development of differentiated properties of RPE cells in in vitro culture studies [38,[43][44][45]. In IF assays, HTERT-RPE cells grown to confluence on glass and ABC with UBM ( Fig.…”

Section: Rpe Cell Morphologymentioning

confidence: 99%

Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium

Gonçalves

Rodrigues

Padrão

et al. 2016

Colloids and Surfaces B: Biointerfaces

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This work evaluated the effect of acetylated bacterial cellulose (ABC) substrates coated with urinary bladder matrix (UBM) on the behavior of retinal pigment epithelium (RPE), as assessed by cell adhesion, proliferation and development of cell polarity exhibiting transepithelial resistance and polygonal shaped-cells with microvilli. Acetylation of bacterial cellulose (BC) generated a moderate hydrophobic surface (around 65°) while the adsorption of UBM onto these acetylated substrates did not affect significantly the surface hydrophobicity. The ABS substrates coated with UBM enabled the development of a cell phenotype closer to that of native RPE cells. These cells were able to express proteins essential for their cytoskeletal organization and metabolic function (ZO-1 and RPE65), while showing a polygonal shaped morphology with microvilli and a monolayer configuration. The coated ABC substrates were also characterized, exhibiting low swelling effect (between 1.5-2.0 swelling/mm3), high mechanical strength (2048MPa) and non-pyrogenicity (2.12EU/L). Therefore, the ABC substrates coated with UBM exhibit interesting features as potential cell carriers in RPE transplantation that ought to be further explored. Therefore, the ABC substrates coated with UBM showed a great potential to be applied as cell carriers in RPE transplantation.

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Section: Rpe Cell Morphologymentioning

confidence: 99%

Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium

Gonçalves

Rodrigues

Padrão

et al. 2016

Colloids and Surfaces B: Biointerfaces

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“…The retina provides an optimal system to investigate this potential due to its well-defined and conserved developmental program and the availability of markers to distinguish each major stage of early retinogenesis. In addition, human embryonic stem cells (hESCs) display a propensity to produce cells with retinal characteristics (3,4). One criterion for assessing hESCbased developmental model systems is the capacity to recapitulate the normal maturation sequence present in the embryo in a controlled, stepwise fashion (1,2).…”

mentioning

confidence: 99%

“…To date, hESC studies have focused on the derivation of subsets of retinal cell populations, with emphasis on the production of either retinal progenitors (5,6) or more mature cells such as retinal pigment epithelium (RPE) (3,4) or photoreceptors (7). Many of these studies used various exogenous factors to increase the percentage of early retinal cell types present within the mixed population of differentiating hESCs.…”

mentioning

confidence: 99%

Modeling early retinal development with human embryonic and induced pluripotent stem cells

Meyer¹,

Shearer²,

Capowski³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

552

592

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Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis. Upon differentiation, hESCs initially yielded a highly enriched population of early eye field cells. Thereafter, a subset of cells acquired features of advancing retinal differentiation in a sequence and time course that mimicked in vivo human retinal development. Application of this culture method to a human iPS cell line also generated retina-specific cell types at comparable times in vitro. Lastly, altering endogenous signaling during differentiation affected lineage-specific gene expression in a manner consistent with established mechanisms of early neural and retinal cell fate determination. These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells.

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“…38,39 The use of ES-RPE cells holds promise in that a large number of cell monolayers could be generated to potentially supply the necessary graft volume required for large-scale therapy, while avoiding any genetic defects inherent in autologous RPE. 38,40 However, the problem of rejection still needs to be fully solved.…”

Section: Stem Cellsmentioning

confidence: 99%

Replacement of the RPE monolayer

Sheridan

Mason

Pattwell

et al. 2009

Eye

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There are numerous scenarios in which replacing the diseased RPE monolayer is an attractive but as yet unrealised goal. The proof of concept that vision can be improved by placing a healthy neuroretina onto a different, healthy, underlying RPE layer is demonstrated in patch graft transplantations. The surgical procedure to relocate the neuroretina is both complex and is hampered by postoperative complications and as such newer replacement procedures are also being investigated including stem cell replacement therapies. Past studies have largely focused on using cell suspensions and have had disappointing outcomes largely due to the lack of control over cellular differentiation, incomplete attachment onto Bruch's membrane and subsequent integration into the existing RPE monolayer. The choice of which cells to transplant is still under investigation and is complicated by factors such as the ease of collection of an adequate sample, rejection following implantation, the age of the cells and ethical issues. In all these situations, however, understanding the mechanisms of cellular differentiation are likely to be prerequisite to future successes. The current research into replacing the RPE monolayer is briefly discussed with reference to our experiences comparing IPE and RPE cells in an in vitro environment.

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Elucidating the phenomenon of HESC-derived RPE: Anatomy of cell genesis, expansion and retinal transplantation

Cited by 248 publications

References 66 publications

Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium

Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium

Modeling early retinal development with human embryonic and induced pluripotent stem cells

Replacement of the RPE monolayer

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