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 (scRNA-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 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.
Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells
Disclosures: J.D. Manos is currently an employee at AbbVie. G. Prusky is the president of CerebralMechanics Inc. Equipment used in the study was manufactured by CerebralMechanics. She had no influence on how the data the study was generated. S. Temple reported a patent to US8481313B2 issued; and is a co-founder of LUXA Biotechnology, which is advancing RPE transplantation for patients with dry age-related macular degeneration (AMD). J.H. Stern is an officer of Luxa Biotechnology, which is advancing retinal pigment epithelial cell transplantation therapy for dry age-related macular degeneration. No other disclosures were reported.
J.D. Manos’s current affiliation is Abbvie, Cambridge Research Center, Cambridge, MA, USA.
C. Zhao’s current affiliation is Regeneron Pharmaceuticals, Rensselaer, NY, USA.
- Award Id(s): R01EY032138,R01EY029281,U01EY030581
- Award Id(s): C028504
Farhad Farjood, Justine D. Manos, Yue Wang, Anne L. Williams, Cuiping Zhao, Susan Borden, Nazia Alam, Glen Prusky, Sally Temple, Jeffrey H. Stern, Nathan C. Boles; Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells. J Exp Med 4 December 2023; 220 (12): e20230913. doi: https://doi.org/10.1084/jem.20230913
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