title: Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies.
abstract: Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Institut de Microcirurgia Ocular (IMO), Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Riera
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR) , Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontrodona
authors.affiliation: Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Silvia
authors.initials: S
authors.lastname: Albert
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Department of Surgery, Faculty of Medicine, Universitat Autònoma de Barcelona Bellaterra, Spain.
authors.forename: Diana Mora
authors.initials: DM
authors.lastname: Ramirez
authors.affiliation: Center of Regenerative Medicine in Barcelona (CMRB) , Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Seriola
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR) , Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Salas
authors.affiliation: Center of Regenerative Medicine in Barcelona (CMRB) , Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Muñoz
authors.affiliation: Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain; CIISA, Faculdade de Medicina Veterinaria, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.affiliation: Ophthalmology Department, Faculty of Medicine, Universidad de Murcia , Murcia, Spain.
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Villegas-Perez
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR) , Barcelona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Zapata
authors.affiliation: Center of Regenerative Medicine in Barcelona (CMRB), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Raya
authors.affiliation: Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain; CIISA, Faculdade de Medicina Veterinaria, Universidade de Lisboa, Lisboa, Portugal; Department of Anatomy and Animal Health, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Ruberte
authors.affiliation: Center of Regenerative Medicine in Barcelona (CMRB) , Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Veiga
authors.affiliation: Ophthalmology Research, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Institut de Microcirurgia Ocular (IMO), Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Garcia-Arumi