Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration

被引:27
作者
Mitrousis, Nikolaos [1 ,2 ]
Hacibekiroglu, Sabiha [3 ,4 ]
Ho, Margaret T. [1 ,2 ]
Sauve, Yves [5 ]
Nagy, Andras [3 ,4 ,6 ]
van der Kooy, Derek [2 ,4 ,7 ]
Shoichet, Molly S. [1 ,2 ,4 ,8 ,9 ]
机构
[1] Univ Toronto, Inst Biomed Engn, Toronto, ON M5S 3G9, Canada
[2] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada
[3] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
[5] Univ Alberta, Dept Ophthalmol & Visual Sci, Edmonton, AB T6G 2R7, Canada
[6] Univ Toronto, Dept Obstet & Gynaecol, Toronto, ON M5G 1E2, Canada
[7] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[8] Univ Toronto, Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada
[9] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Hydrogel; Retinal regeneration; RPE; Co-transplantation; Photoreceptors; Blindness; EMBRYONIC STEM-CELLS; VISUAL FUNCTION; SODIUM IODATE; SUBRETINAL IMPLANTATION; ROD PHOTORECEPTORS; PROTECTS CONE; MOUSE MODEL; DIFFERENTIATION; EXPRESSION; INTEGRATION;
D O I
10.1016/j.biomaterials.2020.120233
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
We demonstrate a novel approach to reverse advanced stages of blindness using hydrogel-mediated delivery of retinal pigmented epithelium (RPE) and photoreceptors directly to the degenerated retina of blind mice. With sodium iodate (NaIO3) injections in mice, both RPE and photoreceptors degenerate, resulting in complete blindness and recapitulating the advanced retinal degeneration that is often observed in humans. We observed vision restoration only with co-transplantation of RPE and photoreceptors in a hyaluronic acid-based hydrogel, and not with transplantation of each cell type alone as determined with optokinetic head tracking and light avoidance assays. Both RPE and photoreceptors survived significantly better when co-transplanted than in their respective single cell type controls. While others have pursued transplantation of one of either RPE or photoreceptors, we demonstrate the importance of transplanting both cell types with a minimally-invasive hydrogel for vision repair in a degenerative disease model of the retina.
引用
收藏
页数:14
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