Hiroyuki Kamao1, Michiko Mandai2, Wataru Ohashi3, Yasuhiko Hirami4, Yasuo Kurimoto4, Junichi Kiryu5, Masayo Takahashi2. 1. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo, Japan 2Department of Ophthalmology, Kawasaki Medical School, Kurashiki, Okayama, Japan. 2. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo, Japan. 3. Japan Animal Care Corporation, Meguro, Tokyo, Japan. 4. Institute of Biomedical Research and Innovation Hospital, Chuo-ku, Kobe, Hyogo, Japan. 5. Department of Ophthalmology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Abstract
Purpose: To develop a clinically applicable transplantation device and surgical procedure for extracellular matrix-scaffold-supported human-induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) cell sheet transplantation for clinical use. Methods: The developed surgical device consisted of a custom-designed hand piece and a cannula. The subretinal transplantation of hiPSC-RPE cell sheets was performed in 12 rabbits. The results evaluated were the graft condition (damage or fold), side (front or back), position (center, near, far), and direction (anterior, posterior, right, left) immediately after surgery and the graft condition (shrinking or fold) 2 weeks after surgery. These results were evaluated by fundus photography and optical coherence tomography, followed by immersion-fixed histology. Results: All grafts could be transplanted without obvious damage. The transplanted grafts included 2 of 12 folded grafts, 12 of 12 front side, 12 of 12 center position, 10 of 12 anterior direction, and 2 of 12 right direction immediately after surgery, whereas transplantation with a distance between an inlet and an outlet greater than graft and the coaxial direction of the flow paths and the insertion device posed the correct condition and direction. Two weeks after the surgery, the transplanted grafts included two folded grafts and four shrunken grafts; however, complete drainage of subretinal fluid for adhesion between the graft and the host prevented shrunken grafts. Conclusions: A developed surgical device and procedure allow grafts to be transplanted into the targeted transplantation site safely and reproducibly. This surgical method will provide additional information on the advancement of future RPE transplantation therapies.
Purpose: To develop a clinically applicable transplantation device and surgical procedure for extracellular matrix-scaffold-supported human-induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) cell sheet transplantation for clinical use. Methods: The developed surgical device consisted of a custom-designed hand piece and a cannula. The subretinal transplantation of hiPSC-RPE cell sheets was performed in 12 rabbits. The results evaluated were the graft condition (damage or fold), side (front or back), position (center, near, far), and direction (anterior, posterior, right, left) immediately after surgery and the graft condition (shrinking or fold) 2 weeks after surgery. These results were evaluated by fundus photography and optical coherence tomography, followed by immersion-fixed histology. Results: All grafts could be transplanted without obvious damage. The transplanted grafts included 2 of 12 folded grafts, 12 of 12 front side, 12 of 12 center position, 10 of 12 anterior direction, and 2 of 12 right direction immediately after surgery, whereas transplantation with a distance between an inlet and an outlet greater than graft and the coaxial direction of the flow paths and the insertion device posed the correct condition and direction. Two weeks after the surgery, the transplanted grafts included two folded grafts and four shrunken grafts; however, complete drainage of subretinal fluid for adhesion between the graft and the host prevented shrunken grafts. Conclusions: A developed surgical device and procedure allow grafts to be transplanted into the targeted transplantation site safely and reproducibly. This surgical method will provide additional information on the advancement of future RPE transplantation therapies.
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