Biju B Thomas1, Danhong Zhu2, Li Zhang3, Padmaja B Thomas4, Yuntao Hu5, Hossein Nazari6, Francisco Stefanini6, Paulo Falabella6, Dennis O Clegg7, David R Hinton2, Mark S Humayun1. 1. 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. 2. 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. 3. Eye Center, Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China. 4. Cellular Therapies Production Center, City of Hope, Duarte, California, United States. 5. Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, Tsinghua University Medical Center, Beijing, China. 6. Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, California, United States. 7. Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, California, United States.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunctionrat model.
Authors: Biju B Thomas; Danhong Zhu; Tai-Chi Lin; Young Chang Kim; Magdalene J Seiler; Juan Carlos Martinez-Camarillo; Bin Lin; Yousuf Shad; David R Hinton; Mark S Humayun Journal: Graefes Arch Clin Exp Ophthalmol Date: 2018-09-13 Impact factor: 3.117
Authors: Mandeep S Singh; Susanna S Park; Thomas A Albini; M Valeria Canto-Soler; Henry Klassen; Robert E MacLaren; Masayo Takahashi; Aaron Nagiel; Steven D Schwartz; Kapil Bharti Journal: Prog Retin Eye Res Date: 2019-09-05 Impact factor: 21.198
Authors: Tai-Chi Lin; Magdalene J Seiler; Danhong Zhu; Paulo Falabella; David R Hinton; Dennis O Clegg; Mark S Humayun; Biju B Thomas Journal: Stem Cells Int Date: 2017-08-27 Impact factor: 5.443
Authors: Damien G Harkin; Siobhan E Dunphy; Audra M A Shadforth; Rebecca A Dawson; Jennifer Walshe; Nadia Zakaria Journal: Cell Transplant Date: 2017-11 Impact factor: 4.064
Authors: Trevor J McGill; Osnat Bohana-Kashtan; Jonathan W Stoddard; Michael D Andrews; Neelay Pandit; Lior R Rosenberg-Belmaker; Ofer Wiser; Limor Matzrafi; Eyal Banin; Benjamin Reubinoff; Nir Netzer; Charles Irving Journal: Transl Vis Sci Technol Date: 2017-06-14 Impact factor: 3.283