2026-04-05T10:39:59Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/75652024-12-13T10:36:35Zcom_2072_378071com_2072_378040col_2072_378097
RECERCAT
author
Isla Magrané, Helena
author
Veiga, Anna
author
García Arumí, José
author
Duarri Piqué, Anna
2023-11-08T15:10:30Z
2023-11-08T15:10:30Z
2022-05-23T08:25:36Z2022-05-23T08:25:36Z2021-11-22
http://hdl.handle.net/11351/7565
Cornea; Ocular organoids; Ocular precursor cellsCórnea; Organoides oculares; Células precursoras ocularesCòrnia; Organoides oculars; Cèl·lules precursores ocularsBackground
Recently, great efforts have been made to design protocols for obtaining ocular cells from human stem cells to model diseases or for regenerative purposes. Current protocols generally focus on isolating retinal cells, retinal pigment epithelium (RPE), or corneal cells and fail to recapitulate the complexity of the tissue during eye development. Here, the generation of more advanced in vitro multiocular organoids from human induced pluripotent stem cells (hiPSCs) is demonstrated.
Methods
A 2-step method was established to first obtain self-organized multizone ocular progenitor cells (mzOPCs) from 2D hiPSC cultures within three weeks. Then, after the cells were manually isolated and grown in suspension, 3D multiocular organoids were generated to model important cellular features of developing eyes.
Results
In the 2D culture, self-formed mzOPCs spanned the neuroectoderm, surface ectoderm, neural crest, and RPE, mimicking early stages of eye development. After lifting, mzOPCs developed into different 3D multiocular organoids composed of multiple cell lineages including RPE, retina, and cornea, and interactions between the different cell types and regions of the eye system were observed. Within these organoids, the retinal regions exhibited correct layering and contained all major retinal cell subtypes as well as retinal morphological cues, whereas the corneal regions closely resembled the transparent ocular-surface epithelium and contained of corneal, limbal, and conjunctival epithelial cells. The arrangement of RPE cells also formed organoids composed of polarized pigmented epithelial cells at the surface that were completely filled with collagen matrix.
Conclusions
This approach clearly demonstrated the advantages of the combined 2D-3D construction tissue model as it provided a more ocular native-like cellular environment than that of previous models. In this complex preparations, multiocular organoids may be used to model the crosstalk between different cell types in eye development and disease.This research project was funded by a grant from La Marató de TV3 Foundation (484/C/2012) and ERA-NET EuroNanoMed III/ISCIII (AC19/00080) (CELLUX). We thank CERCA Program/Generalitat de Catalunya for institutional support (SGR 2017–2019). A.D. was supported by PRB2-ISCIII (PT13/0001/0041) and ISCIII-FEDER RETICS (Oftared; RD16/0008). H.IM. was supported by EuroNanoMed III-ISCIII (AC19/00080).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Diferenciació cel·lular
Ulls - Malalties
Medicina regenerativa
ANATOMY::Sense Organs::Eye::Pigment Epithelium of Eye::Retinal Pigment Epithelium
ANATOMY::Cells::Stem Cells::Adult Stem Cells::Induced Pluripotent Stem Cells
PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Differentiation
ANATOMÍA::órganos de los sentidos::ojo::epitelio pigmentado ocular::epitelio pigmentado de la retina
ANATOMÍA::células::células madre::células madre adultas::células madre pluripotentes inducidas
FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::diferenciación celular
Multiocular organoids from human induced pluripotent stem cells displayed retinal, corneal, and retinal pigment epithelium lineages
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion