PMID- 31009651 OWN - NLM STAT- MEDLINE DCOM- 20200213 LR - 20200213 IS - 1096-0295 (Electronic) IS - 0273-2300 (Linking) VI - 106 DP - 2019 Aug TI - Subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelium (MA09-hRPE): A safety and tolerability evaluation in minipigs. PG - 7-14 LID - S0273-2300(19)30105-9 [pii] LID - 10.1016/j.yrtph.2019.04.006 [doi] AB - This study aimed to determine the safety and tolerability of the subretinal injection of hESC-derived RPE cells at higher doses than the established clinical dose (5 x 10(4) cells/150 muL) by using minipigs. The hESC-derived RPE cells (60 or 120 x 10(4) cells/150 muL) were injected in subretinal region, and minipigs were sacrificed at Weeks 4, 8, and 12 post-surgery. Time-course examination was performed by using fundus photography, optical coherence tomography (OCT), histopathology, and fluorescence in situ hybridization (FISH). After surgery, retinal bleb and pigmentation were seen and retinal bleb became smaller gradually. In histopathology, cell clusters consisting of a uniform population of the round to oval cells were seen at the subretinal injection site. In immunohistochemistry, most of the cells were positive for anti-CD3 and CD45 antibodies but negative for anti-human nuclei antibody; transplanted cells were not detectable by DNA probe in FISH assay. Cell clusters were thought to be a host immune response to trauma or transplanted cells. There were no other changes related to subretinal RPE cell injection. These results suggested that subretinal injection of hESC-derived RPE cells (60 and 120 x 10(4) cells/150 muL) in minipigs is well-tolerated and safe. CI - Copyright (c) 2019. Published by Elsevier Inc. FAU - Cho, Sung-Min AU - Cho SM AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: somnium14@naver.com. FAU - Lee, Junyeop AU - Lee J AD - Department of Ophthalmology, Yeungnam University, College of Medicine, 170, Hyeonchung-ro, Nam-gu, Daegu, Republic of Korea. Electronic address: retina@yu.ac.kr. FAU - Lee, Han-Byul AU - Lee HB AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: onestar0620@naver.com. FAU - Choi, Hyun-Ji AU - Choi HJ AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: snapple08@naver.com. FAU - Ryu, Jae-Eun AU - Ryu JE AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: bangarje@naver.com. FAU - Lee, Hyo-Ju AU - Lee HJ AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: hyoju_lee@daum.net. FAU - Park, Hyun-Kyu AU - Park HK AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: nevok@hanmail.net. FAU - Lee, Min Ji AU - Lee MJ AD - CHA Biotech, 335, Pangyo-ro, Bundang-gu, Seongnam, Republic of Korea. Electronic address: minjilee@gmail.com. FAU - Lee, Juyoung AU - Lee J AD - CHA Biotech, 335, Pangyo-ro, Bundang-gu, Seongnam, Republic of Korea. Electronic address: suniv84@hanmail.net. FAU - Lee, Hyun Jung AU - Lee HJ AD - CHA Biotech, 335, Pangyo-ro, Bundang-gu, Seongnam, Republic of Korea. Electronic address: hjlee4993@gmail.com. FAU - Kim, Hye Sun AU - Kim HS AD - CHA Biotech, 335, Pangyo-ro, Bundang-gu, Seongnam, Republic of Korea. Electronic address: hyesunkim98@gmail.com. FAU - Lee, Joo Yong AU - Lee JY AD - Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: ophthalmo@amc.seoul.kr. FAU - Son, Woo-Chan AU - Son WC AD - Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea. Electronic address: wcson@amc.seoul.kr. LA - eng PT - Journal Article DEP - 20190419 PL - Netherlands TA - Regul Toxicol Pharmacol JT - Regulatory toxicology and pharmacology : RTP JID - 8214983 SB - IM MH - Animals MH - Human Embryonic Stem Cells/*cytology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Retinal Pigment Epithelium/*cytology/*transplantation MH - *Safety MH - Swine MH - *Swine, Miniature MH - Tomography, Optical Coherence OTO - NOTNLM OT - Age-related macular degeneration OT - Minipig OT - Preclinical study OT - Subretinal injection OT - hESC-derived RPE cell EDAT- 2019/04/23 06:00 MHDA- 2020/02/14 06:00 CRDT- 2019/04/23 06:00 PHST- 2018/06/01 00:00 [received] PHST- 2019/04/10 00:00 [revised] PHST- 2019/04/14 00:00 [accepted] PHST- 2019/04/23 06:00 [pubmed] PHST- 2020/02/14 06:00 [medline] PHST- 2019/04/23 06:00 [entrez] AID - S0273-2300(19)30105-9 [pii] AID - 10.1016/j.yrtph.2019.04.006 [doi] PST - ppublish SO - Regul Toxicol Pharmacol. 2019 Aug;106:7-14. doi: 10.1016/j.yrtph.2019.04.006. Epub 2019 Apr 19.