Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Idelson, Masha; Alper, Ruslana; Obolensky, Alexey; Yachimovich-Cohen, Nurit; Rachmilewitz, Jacob; Ejzenberg, Ayala; Beider, Ekaterina; Banin, Eyal; Reubinoff, Benjamin

doi:10.1016/j.stemcr.2018.07.009

Cited by 38 publications

(35 citation statements)

References 36 publications

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“…Subgroup analysis was not conducted for awave amplitudes because the subgroups contained too few studies in order to draw meaningful conclusions (less than 4 studies per subgroup remained). For the meta-analysis of ERG b-wave amplitude, twelve [25,29,30,32,33,35,[39][40][41]44,45,49] studies reporting 42 experiments were included, of which 30 experiments were performed in rats and 12 in mice. See Supplementary 1 for all study characteristics of the individual studies.…”

Section: A-wave and B-wave Amplitudes Extracted From Erg Datamentioning

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: A-wave and B-wave Amplitudes Extracted From Erg Datamentioning

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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“…IPSCs derived from healthy donors have demonstrated the ability to suppress T-cell activation, induce T-regulatory cells, and secrete immune suppressive factors such as MIF and TGFβ (Sugita et al, 2015). HESCs have also indicated a similar capacity, and appear to have a better immunomodulatory response in the absence of immune suppressive drugs, such as cyclosporine (Idelson et al, 2018).…”

Section: Transplantation and Factors Affecting Integrationmentioning

confidence: 99%

Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

Ikelle

Al‐Ubaidi

Naash

2020

Front. Cell Dev. Biol.

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Stem cells have been part of the biomedical landscape since the early 1960s. However, the translation of stem cells to effective therapeutics have met significant challenges, especially for retinal diseases. The retina is a delicate and complex architecture of interconnected cells that are steadfastly interdependent. Degenerative mechanisms caused by acquired or inherited diseases disrupt this interconnectivity, devastating the retina and causing severe vision loss in many patients. Consequently, retinal differentiation of exogenous and endogenous stem cells is currently being explored as replacement therapies in the debilitating diseases. In this review, we will examine the mechanisms involved in exogenous stem cells differentiation and the challenges of effective integration to the host retina. Furthermore, we will explore the current advancements in trans-differentiation of endogenous stem cells, primarily Müller glia.

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“…We showed that iPSC-RGCs suppressed the immune activity of T-cells via TGF-β. Human corneal endothelial cells, iris pigment epithelial cells and stem cell-derived RPEs have been reported to suppress T-cell activation via TGF-β [4,6,43,44]. In particular, it has been suggested that the induction of regulatory T-cells by TGF-β is involved in the mechanism of inhibition by human corneal endothelial cells and iPSC-RPEs [4,44].…”

Section: Discussionmentioning

confidence: 99%

“…Retinal ganglion cells (RGCs), which are located in the innermost layer of the retina, are responsible for collecting optical information that reaches the retina, and transmitting it to the brain via the optic nerve [ 1 ]. Retinal pigment epithelial cells (RPEs), which are one of the constituent cells of the retina as well as RGCs, have been reported to possess immune-suppression capacity [ 2 , 3 , 4 , 5 , 6 ]. Stem cell-derived RPE transplantation therapy has already been applied clinically [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

Edo

Sugita

Futatsugi

et al. 2020

IJMS

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Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.

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Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Cited by 38 publications

References 36 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

Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

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