The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

Davis, R. J.; Alam, Nazia M.; Zhao, Chuanzhi; Müller, Claudia; Saini, Janmeet S.; Blenkinsop, Timothy A.; Mazzoni, Francesca; Campbell, Melissa; Borden, Susan; Charniga, Carol; Lederman, Patty; Aguilar, Vanessa; Naimark, Michael; Fiske, Michael; Boles, Nathan C.; Temple, Sally; Finnemann, Silvia C.; Prusky, Glen T.; Stern, Jeffrey H.

doi:10.1016/j.stemcr.2017.05.016

Cited by 57 publications

(66 citation statements)

References 30 publications

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“…and additional statistics data (individual Hedges' g, lower-and upper limits) can be found in Table S6. Sixteen studies [26][27][28]31,[34][35][36][37][38][39][41][42][43][46][47][48] reporting 96 experiments were included in the meta-analysis. Ninety-one studies were performed in rats and five in mice.…”

Section: Behavioral Assaysmentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

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The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used. Methods: In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a-and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. Results: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave Int.(Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 5 versus in the range o...

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Section: Behavioral Assaysmentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

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“…25,26 In the early stages of age-related macular degeneration, before photoreceptors are fully lost, dysfunctional RPE has been replaced and sight restored in animals by transplanting new RPE cells into the macula. 27 At later stages of age-related macular degeneration, cell therapy would require the transplantation of photoreceptor cells (or cells that could differentiate into photoreceptor cells), in addition to the RPE cells.…”

Section: The E Y Ementioning

confidence: 99%

Stem Cells in the Treatment of Disease

2019

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“…They are also prone to tumour formation and immune rejection (Lee, Tang, Rao, Irving, & Wu, ; Xian & Huang, ) and therefore could potentially cause safety and long‐term cell survival concerns (Carr et al, ; Diniz et al, ; Lu et al, ; Nakano‐Okuno, Borah, & Nakano, ; Westenskow et al, ). A newer source of human RPE cell is the adult RPESCs, which are not tumorigenic (Salero et al, ) and show great potential to preserve vision based on preclinical studies (Blenkinsop et al, ; Davis et al, ; Davis et al, ; Stanzel et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Following, it was shown that subretinal injection of a suspension of RPESC‐RPE cells is efficacious at preventing vision loss in the Royal College of Surgeons rat model of retinal degeneration (Davis et al, ). Notably, a particular intermediate stage of the RPESC‐RPE cell product was found to be most efficacious at preserving vision in this model (Davis et al, ).…”

Section: Introductionmentioning

confidence: 87%

Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation

Tian

Davis

Zonca

et al. 2018

J Tissue Eng Regen Med

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Retinal pigment epithelial (RPE) cells are highly specialized neural cells that have several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and ultimately the blinding disease agerelated macular degeneration. Subretinal transplantation of stem cell-derived RPE cell suspensions is being explored as a strategy to recover the damaged retina and improve vision. This approach may be improved by developing a vehicle that increases postinjection cell viability and distribution and integration of RPE cells. In this study, Food and Drug Administration-approved natural polymers, including alginate, methylcellulose, and hyaluronic acid (HA), were examined for performance as cell vehicles for adult human RPE stem cells (RPESCs). We compared the effect of RPESC storage as a cell suspension in these delivery vehicles for 1-96 hr at different temperatures on subsequent cell performance in a cell culture model. RPESC survival, attachment, distribution, proliferation, and differentiation into RPE cells were monitored by microscopy over the course of 8 weeks. Our in vitro results demonstrate that RPESC suspension in a 0.2% HA solution promotes better initial cell distribution, proliferation, cobblestone formation, and expression of RPE cell markers (microphthalmiaassociated transcription factor and orthodenticle homeobox 2) after 96 hr of storage.These data suggest that HA addition to the vehicle can significantly enhance RPESC performance in vitro and is a promising strategy to pursue an improved delivery vehicle supporting in vivo RPE cell transplantation.

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The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

Cited by 57 publications

References 30 publications

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Stem Cells in the Treatment of Disease

Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation

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