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 |
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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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