PMID- 34314890
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 134
DP  - 2021 Oct 15
TI  - Biodegradable scaffolds facilitate epiretinal transplantation of hiPSC-Derived 
      retinal neurons in nonhuman primates.
PG  - 289-301
LID - S1742-7061(21)00478-5 [pii]
LID - 10.1016/j.actbio.2021.07.040 [doi]
AB  - Transplantation of stem cell-derived retinal neurons is a promising regenerative 
      therapy for optic neuropathy. However, significant anatomic differences 
      compromise its efficacy in large animal models. The present study describes the 
      procedure and outcomes of human-induced pluripotent stem cell (hiPSC)-derived 
      retinal sheet transplantation in primate models using biodegradable materials. 
      Stem cell-derived retinal organoids were seeded on polylactic-coglycolic acid 
      (PLGA) scaffolds and directed toward a retinal ganglion cell (RGC) fate. The 
      seeded tissues showed active proliferation, typical neuronal morphology, and 
      electrical excitability. The cellular scaffolds were then epiretinally 
      transplanted onto the inner surface of rhesus monkey retinas. With sufficient 
      graft-host contact provided by the scaffold, the transplanted tissues survived 
      for up to 1 year without tumorigenesis. Histological examinations indicated 
      survival, further maturation, and migration. Moreover, green fluorescent 
      protein-labeled axonal projections toward the host optic nerve were observed. 
      Cryopreserved organoids were also able to survive and migrate after 
      transplantation. Our results suggest the potential efficacy of RGC replacement 
      therapy in the repair of optic neuropathy for the restoration of visual function. 
      STATEMENT OF SIGNIFICANCE: In the present study, we generated a human retinal 
      sheet by seeding hiPSC-retinal organoid-derived RGCs on a biodegradable PLGA 
      scaffold. We transplanted this retinal sheet onto the inner surface of the rhesus 
      monkey retina. With scaffold support, donor cells survive, migrate and project 
      their axons into the host optic nerve. Furthermore, an effective cryopreservation 
      strategy for retinal organoids was developed, and the thawed organoids were also 
      observed to survive and show cell migration after transplantation.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Luo, Ziming
AU  - Luo Z
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Xian, Bikun
AU  - Xian B
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Li, Kang
AU  - Li K
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Li, Kaijing
AU  - Li K
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Yang, Runcai
AU  - Yang R
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Chen, Mengfei
AU  - Chen M
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, 601 N Caroline St, Baltimore, MD 21287, United States.
FAU - Xu, Chaochao
AU  - Xu C
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Tang, Mingjun
AU  - Tang M
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Rong, Huifeng
AU  - Rong H
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Hu, Dongpeng
AU  - Hu D
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Ye, Meifang
AU  - Ye M
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Yang, Sijing
AU  - Yang S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Lu, Shoutao
AU  - Lu S
AD  - Bai Duoan Medical Equipment Company. Qihe Economic Development Zone, Qihe, 
      Dezhou, Shandong 251100, China.
FAU - Zhang, Haijun
AU  - Zhang H
AD  - Bai Duoan Medical Equipment Company. Qihe Economic Development Zone, Qihe, 
      Dezhou, Shandong 251100, China.
FAU - Ge, Jian
AU  - Ge J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China. Electronic address: 
      gejian@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210724
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
SB  - IM
MH  - Animals
MH  - Axons
MH  - *Induced Pluripotent Stem Cells
MH  - Optic Nerve
MH  - Retina
MH  - Retinal Ganglion Cells
OTO - NOTNLM
OT  - Biodegradable scaffold
OT  - Retinal ganglion cell
OT  - Retinal sheet
OT  - Rhesus monkey
OT  - hiPSC
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/07/28 06:00
MHDA- 2021/10/29 06:00
CRDT- 2021/07/27 20:17
PHST- 2021/03/29 00:00 [received]
PHST- 2021/06/30 00:00 [revised]
PHST- 2021/07/20 00:00 [accepted]
PHST- 2021/07/28 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/07/27 20:17 [entrez]
AID - S1742-7061(21)00478-5 [pii]
AID - 10.1016/j.actbio.2021.07.040 [doi]
PST - ppublish
SO  - Acta Biomater. 2021 Oct 15;134:289-301. doi: 10.1016/j.actbio.2021.07.040. Epub 
      2021 Jul 24.