Biomaterial Database

cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates. 2021

Swathi Lingam, and Zengping Liu, and Binxia Yang, and Wendy Wong, and Bhav Harshad Parikh, and Jun Yi Ong, and Debbie Goh, and Daniel Soo Lin Wong, and Queenie Shu Woon Tan, and Gavin S W Tan, and Graham E Holder, and Kakkad Regha, and Veluchamy Amutha Barathi, and Walter Hunziker, and Gopal Lingam, and Xianmin Zeng, and Xinyi Su

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.

Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.

UI	MeSH Term	Description	Entries
D011323	Primates	An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch.	Primate
D012162	Retinal Degeneration	A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)	Degeneration, Retinal,Degenerations, Retinal,Retinal Degenerations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D057026	Induced Pluripotent Stem Cells	Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.	Human Induced Pluripotent Stem Cell,IPS Cell,IPS Cells,Induced Pluripotent Stem Cell,Fibroblast-Derived IPS Cells,Fibroblast-Derived Induced Pluripotent Stem Cells,Human Induced Pluripotent Stem Cells,hiPSC,Cell, Fibroblast-Derived IPS,Cell, IPS,Cells, Fibroblast-Derived IPS,Cells, IPS,Fibroblast Derived IPS Cells,Fibroblast Derived Induced Pluripotent Stem Cells,Fibroblast-Derived IPS Cell,IPS Cell, Fibroblast-Derived,IPS Cells, Fibroblast-Derived
D017949	Retinal Cone Photoreceptor Cells	Photosensitive afferent neurons located primarily within the FOVEA CENTRALIS of the MACULA LUTEA. There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. Retinal cone cells operate in daylight vision (at photopic intensities) providing color recognition and central visual acuity.	Cone Photoreceptors,Cones (Retina),Cone Photoreceptor Cells,Photoreceptors, Cone,Retinal Cone,Retinal Cone Cells,Retinal Cone Photoreceptors,Cell, Cone Photoreceptor,Cell, Retinal Cone,Cells, Cone Photoreceptor,Cells, Retinal Cone,Cone (Retina),Cone Cell, Retinal,Cone Cells, Retinal,Cone Photoreceptor,Cone Photoreceptor Cell,Cone Photoreceptor, Retinal,Cone Photoreceptors, Retinal,Cone, Retinal,Cones, Retinal,Photoreceptor Cell, Cone,Photoreceptor Cells, Cone,Photoreceptor, Cone,Photoreceptor, Retinal Cone,Photoreceptors, Retinal Cone,Retinal Cone Cell,Retinal Cone Photoreceptor,Retinal Cones
D020419	Photoreceptor Cells, Vertebrate	Specialized PHOTOTRANSDUCTION neurons in the vertebrates, such as the RETINAL ROD CELLS and the RETINAL CONE CELLS. Non-visual photoreceptor neurons have been reported in the deep brain, the PINEAL GLAND and organs of the circadian system.	Retinal Photoreceptor Cells,Rods and Cones,Photoreceptors, Retinal,Photoreceptors, Vertebrate,Retinal Photoreceptors,Vertebrate Photoreceptor Cells,Vertebrate Photoreceptors,Cell, Retinal Photoreceptor,Cell, Vertebrate Photoreceptor,Cells, Retinal Photoreceptor,Cells, Vertebrate Photoreceptor,Cones and Rods,Photoreceptor Cell, Retinal,Photoreceptor Cell, Vertebrate,Photoreceptor Cells, Retinal,Photoreceptor, Retinal,Photoreceptor, Vertebrate,Retinal Photoreceptor,Retinal Photoreceptor Cell,Vertebrate Photoreceptor,Vertebrate Photoreceptor Cell