PMID- 36963105
OWN - NLM
STAT- MEDLINE
DCOM- 20230412
LR  - 20230425
IS  - 1758-5090 (Electronic)
IS  - 1758-5082 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Apr 11
TI  - One-stop assembly of adherent 3D retinal organoids from hiPSCs based on 
      3D-printed derived PDMS microwell platform.
LID - 10.1088/1758-5090/acc761 [doi]
AB  - The three-dimensional (3D) retinal organoids (ROs) derived from human induced 
      pluripotent stem cells (hiPSCs), mimicking the growth and development of the 
      human retina, is a promising model for investigating inherited retinal diseasesin 
      vitro. However, the efficient generation of homogenous ROs remains a challenge. 
      Here we introduce a novel polydimethylsiloxane (PDMS) microwell platform 
      containing 62 V-bottom micro-cavities for the ROs differentiation from hiPSCs. 
      The uniform adherent 3D ROs could spontaneously form using neural retina (NR) 
      induction. Our results showed that the complex of NR (expressing VSX2), ciliary 
      margin (CM) (expressing RDH10), and retinal pigment epithelium (RPE) (expressing 
      ZO-1, MITF, and RPE65) developed in the PDMS microwell after the differentiation. 
      It is important to note that ROs in PDMS microwell platforms not only enable 
      one-stop assembly but also maintain homogeneity and mature differentiation over a 
      period of more than 25 weeks without the use of BMP4 and Matrigel. Retinal 
      ganglion cells (expressing BRN3a), amacrine cells (expressing AP2a), horizontal 
      cells (expressing PROX1 and AP2alpha), photoreceptor cells for cone (expressing 
      S-opsin and L/M-opsin) and rod (expressing Rod opsin), bipolar cells (expressing 
      VSX2 and PKCalpha), and Muller glial cells (expressing GS and Sox9) gradually 
      emerged. Furthermore, we replaced fetal bovine serum with human platelet lysate 
      and established a xeno-free culture workflow that facilitates clinical 
      application. Thus, our PDMS microwell platform for one-stop assembly and 
      long-term culture of ROs using a xeno-free workflow is favorable for retinal 
      disease modeling, drug screening, and manufacturing ROs for clinical translation.
CI  - (c) 2023 IOP Publishing Ltd.
FAU - Sun, Xihao
AU  - Sun X
AUID- ORCID: 0000-0002-3470-2006
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Cui, Zekai
AU  - Cui Z
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Liang, Yuqin
AU  - Liang Y
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Duan, Chunwen
AU  - Duan C
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Chan, Hon Fai
AU  - Chan HF
AUID- ORCID: 0000-0003-0573-1251
AD  - Institute for Tissue Engineering and Regenerative Medicine, The Chinese 
      University of Hong Kong, Hong Kong 999077, People's Republic of China.
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Hong Kong 999077, People's Republic of China.
FAU - Mao, Shengru
AU  - Mao S
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Gu, Jianing
AU  - Gu J
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Ding, Chengcheng
AU  - Ding C
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Yang, Xu
AU  - Yang X
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Wang, Qing
AU  - Wang Q
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
FAU - Tang, Shibo
AU  - Tang S
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
AD  - Guangzhou Aier Eye Hospital, Guangzhou, Guangdong 510010, People's Republic of 
      China.
FAU - Chen, Jiansu
AU  - Chen J
AUID- ORCID: 0000-0001-6703-9573
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan 410015, 
      People's Republic of China.
AD  - Aier Eye Institute, Changsha, Hunan 410015, People's Republic of China.
AD  - Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan 
      University, Guangzhou, Guangdong 510632, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230411
PL  - England
TA  - Biofabrication
JT  - Biofabrication
JID - 101521964
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Opsins)
RN  - 0 (Dimethylpolysiloxanes)
SB  - IM
MH  - Humans
MH  - *Induced Pluripotent Stem Cells
MH  - Reactive Oxygen Species
MH  - Retina
MH  - Cell Differentiation
MH  - Organoids
MH  - Opsins
MH  - Dimethylpolysiloxanes
MH  - Printing, Three-Dimensional
OTO - NOTNLM
OT  - PDMS
OT  - human induced pluripotent stem cells
OT  - one-stop culture workflow
OT  - retinal organoids
EDAT- 2023/03/25 06:00
MHDA- 2023/04/12 06:42
CRDT- 2023/03/24 18:32
PHST- 2022/11/30 00:00 [received]
PHST- 2023/03/24 00:00 [accepted]
PHST- 2023/04/12 06:42 [medline]
PHST- 2023/03/25 06:00 [pubmed]
PHST- 2023/03/24 18:32 [entrez]
AID - 10.1088/1758-5090/acc761 [doi]
PST - epublish
SO  - Biofabrication. 2023 Apr 11;15(3). doi: 10.1088/1758-5090/acc761.