title: Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.
abstract: To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats.
  
  
  
  Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity.
  
  
  
  Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity.
  
  
  
  These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States 2USC Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States.
authors.forename: Biju B
authors.initials: BB
authors.lastname: Thomas
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States 3Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States.
authors.forename: Danhong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Eye Center, Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cellular Therapies Production Center, City of Hope, Duarte, California, United States.
authors.forename: Padmaja B
authors.initials: PB
authors.lastname: Thomas
authors.affiliation: Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, Tsinghua University Medical Center, Beijing, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nazari
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States.
authors.forename: Francisco
authors.initials: F
authors.lastname: Stefanini
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States.
authors.forename: Paulo
authors.initials: P
authors.lastname: Falabella
authors.affiliation: Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, California, United States.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Clegg
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States 3Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States 2USC Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Humayun
mesh_terms: D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D011108:Polymers; D051381:Rats; D011922:Rats, Mutant Strains; D012162:Retinal Degeneration / Q000473:pathology* / Q000601:surgery; D055213:Retinal Pigment Epithelium / Q000473:pathology* / Q000503:physiopathology; D033581:Stem Cell Transplantation; D041623:Tomography, Optical Coherence
chemical_list: D011108:Polymers