Transplantation of Human Embryonic Stem Cell-Derived Retinal Tissue in the Subretinal Space of the Cat Eye

Autor: Igor O. Nasonkin, Simon M. Petersen-Jones, Francois Binette, Ratnesh K. Singh, Laurence M. Occelli
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Retinal degeneration
Doublecortin Domain Proteins
Pathology
genetic structures
medicine.medical_treatment
Human Embryonic Stem Cells
Vitrectomy
chemistry.chemical_compound
0302 clinical medicine
Original Research Reports
Cellular Reprogramming Techniques
Cells
Cultured
biology
Graft Survival
Cell Differentiation
Hematology
medicine.anatomical_structure
Calbindin 2
Immunohistochemistry
Microtubule-Associated Proteins
Pars plana
medicine.medical_specialty
Doublecortin Protein
retinal organoids
large-eye animal models
Synaptophysin
subretinal transplantation
Retina
Cell Line
03 medical and health sciences
medicine
Animals
Humans
synaptic connectivity
Neuropeptides
Retinal
Cell Biology
medicine.disease
eye diseases
Transplantation
030104 developmental biology
chemistry
biology.protein
Cats
vision restoration
030217 neurology & neurosurgery
Developmental Biology
Stem Cell Transplantation
Zdroj: Stem Cells and Development
ISSN: 1557-8534
1547-3287
Popis: To develop biological approaches to restore vision, we developed a method of transplanting stem cell-derived retinal tissue into the subretinal space of a large-eye animal model (cat). Human embryonic stem cells (hESC) were differentiated to retinal organoids in a dish. hESC-derived retinal tissue was introduced into the subretinal space of wild-type cats following a pars plana vitrectomy. The cats were systemically immunosuppressed with either prednisolone or prednisolone plus cyclosporine A. The eyes were examined by fundoscopy and spectral-domain optical coherence tomography imaging for adverse effects due to the presence of the subretinal grafts. Immunohistochemistry was done with antibodies to retinal and human markers to delineate graft survival, differentiation, and integration into cat retina. We successfully delivered hESC-derived retinal tissue into the subretinal space of the cat eye. We observed strong infiltration of immune cells in the graft and surrounding tissue in the cats treated with prednisolone. In contrast, we showed better survival and low immune response to the graft in cats treated with prednisolone plus cyclosporine A. Immunohistochemistry with antibodies (STEM121, CALB2, DCX, and SMI-312) revealed large number of graft-derived fibers connecting the graft and the host. We also show presence of human-specific synaptophysin puncta in the cat retina. This work demonstrates feasibility of engrafting hESC-derived retinal tissue into the subretinal space of large-eye animal models. Transplanting retinal tissue in degenerating cat retina will enable rapid development of preclinical in vivo work focused on vision restoration.
Databáze: OpenAIRE
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