Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation

Petrus‐Reurer, Sandra; Lederer, Alex R; Baqué-Vidal, Laura; Douagi, Iyadh; Pannagel, Belinda; Khven, Irina; Aronsson, Monica; Bartuma, Hammurabi; Wagner, Magdalena; Wrona, Andreas; Efstathopoulos, Paschalis; Jaberi, Elham; Willenbrock, Hanni; Shimizu, Yutaka; Villaescusa, J. Carlos; André, Helder; Sundström, Erik; Bhaduri, Aparna; Kriegstein, Arnold R.; Kvanta, Anders; Manno, Gioele La; Lanner, Fredrik

doi:10.1016/j.stemcr.2022.05.005

Cited by 14 publications

(6 citation statements)

References 38 publications

(55 reference statements)

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“…This transcriptomic analysis identified 13 subpopulations within the RPESC-RPE cultures with distinct patterns of gene expression, consistent with recent findings from other laboratories (Petrus-Reurer et al, 2022; Xu et al, 2021). Three clusters, 10, 6 and 2, demonstrated enrichment for pathways associated with cell differentiation and proliferation implying that these subpopulations had progenitor characteristics and were candidates to improve both cell manufacture and transplant success.…”

Section: Discussionsupporting

confidence: 91%

“…Our present transcriptomic analysis demonstrated an incomplete ability to separate the RPE cell transcriptomic profiles based solely on time, pointing out the need to dissect RPE cellular heterogeneity at each timepoint. Recent studies using single cell approaches have reported multiple RPE subpopulations within the stem cell-derived, native human and mouse RPE with unique transcriptional and morphological characteristics, indicating that the RPE cell layer is composed of heterogenous cell populations that may have differing functional and clinical capabilities (Lee et al, 2022; Petrus-Reurer et al, 2022; Voigt et al, 2019; Xu et al, 2021). Identification of the subpopulations responsible for vision rescue can improve regulatory evaluation and improve RPE cell products to result in better transplantation outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

Farjood

Manos²,

Wang

et al. 2022

Preprint

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Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single cell RNA sequencing (sc-RNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed a lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

Farjood

Manos²,

Wang

et al. 2022

Preprint

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“…Furthermore, none of the protocols can currently generate retinal pigment epithelium (RPEs), which is a clear shortcoming of the protocols. Future benchmarking efforts will require the incorporation of studies that generate single-cell transcriptomic profiles of RPEs across development ( Hu et al., 2019 ; Petrus-Reurer et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

et al. 2023

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“…As such, further research using both cell types is warranted to evaluate the safety and practicality of both forms of transplantation. With advances in molecular profiling of stem cell-derived RPE cells ( Petrus-Reurer et al, 2022 ), safety and efficacy measures are improving, thereby, further supporting the feasibility of transplantation approaches.…”

Section: Recent Findingsmentioning

confidence: 99%

Stem cell-derived retinal pigment epithelium cell therapy: Past and future directions

Rohowetz

Koulen

2023

Front. Cell Dev. Biol.

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The eyes are relatively immune privileged organs, making them ideal targets for stem cell therapy. Researchers have recently developed and described straightforward protocols for differentiating embryonic and induced pluripotent stem cells into retinal pigment epithelium (RPE), making diseases affecting the RPE, such as age-related macular degeneration (AMD), viable targets for stem cell therapy. With the advent of optical coherence tomography, microperimetry, and various other diagnostic technologies, the ability to document disease progression and monitor response to treatments such as stem cell therapy has been significantly enhanced in recent years. Previous phase I/II clinical trials have employed various cell origins, transplant methods, and surgical techniques to identify safe and efficacious methods of RPE transplantation, and many more are currently underway. Indeed, findings from these studies have been promising and future carefully devised clinical trials will continue to enhance our understanding of the most effective methods of RPE-based stem cell therapy, with the hope to eventually identify treatments for disabling and currently incurable retinal diseases. The purpose of this review is to briefly outline existing outcomes from initial clinical trials, review recent developments, and discuss future directions of clinical research involving stem-cell derived RPE cell transplantation for retinal disease.

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Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation

Cited by 14 publications

References 38 publications

Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

Identifying Biomarkers of Retinal Pigment Epithelial Cell Stem Cell-derived RPE Cell Heterogeneity and Transplantation Efficacy

Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids

Stem cell-derived retinal pigment epithelium cell therapy: Past and future directions

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