Sonia Labrador Velandia1,2, Salvatore Di Lauro1,2, Maria Luz Alonso-Alonso1, Soraya Tabera Bartolomé3, Girish Kumar Srivastava1,4,5, José Carlos Pastor1,2,4,5, Ivan Fernandez-Bueno6,7,8. 1. Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Campus Miguel Delibes, Paseo de Belén 17, 47011, Valladolid, Spain. 2. Department of Ophthalmology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 3. UPC (Cell-production Unit), Instituto de Biología y Genética Molecular (IBGM), University of Valladolid and Centro Superior de Investigaciones Científicas (CSIC), Valladolid, Spain. 4. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Valladolid, Spain. 5. Red Temática de Investigación Cooperativa en Salud (RETICS), Oftared, Instituto de Salud Carlos III, Valladolid, Spain. 6. Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Campus Miguel Delibes, Paseo de Belén 17, 47011, Valladolid, Spain. ifernandezb@ioba.med.uva.es. 7. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Valladolid, Spain. ifernandezb@ioba.med.uva.es. 8. Red Temática de Investigación Cooperativa en Salud (RETICS), Oftared, Instituto de Salud Carlos III, Valladolid, Spain. ifernandezb@ioba.med.uva.es.
Abstract
PURPOSE: To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits. MATERIALS AND METHODS: Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 106 cells/ml. Groups 3 and 6 received a high dose of 30 × 106 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs. RESULTS: There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected. CONCLUSIONS: MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 106 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.
PURPOSE: To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits. MATERIALS AND METHODS: Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 106 cells/ml. Groups 3 and 6 received a high dose of 30 × 106 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs. RESULTS: There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected. CONCLUSIONS: MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 106 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.
Authors: Beatriz E Ramírez; Ana Sánchez; José M Herreras; Itziar Fernández; Javier García-Sancho; Teresa Nieto-Miguel; Margarita Calonge Journal: Biomed Res Int Date: 2015-09-16 Impact factor: 3.411
Authors: Ricardo Usategui-Martín; Kevin Puertas-Neyra; Nadia Galindo-Cabello; Leticia A Hernández-Rodríguez; Fernando González-Pérez; José Carlos Rodríguez-Cabello; Rogelio González-Sarmiento; José Carlos Pastor; Ivan Fernandez-Bueno Journal: Invest Ophthalmol Vis Sci Date: 2022-04-01 Impact factor: 4.925
Authors: Ricardo Usategui-Martín; Kevin Puertas-Neyra; María-Teresa García-Gutiérrez; Manuel Fuentes; José Carlos Pastor; Ivan Fernandez-Bueno Journal: Mol Ther Methods Clin Dev Date: 2020-05-13 Impact factor: 6.698