| Title: |
Preconditioning the Initial State of Feeder-free Human Pluripotent Stem Cells Promotes Self-formation of Three-dimensional Retinal Tissue |
| Authors: |
Kuwahara, Atsushi; Yamasaki, Suguru; Mandai, Michiko; Watari, Kenji; Matsushita, Keizo; Fujiwara, Masayo; Hori, Yoriko; Hiramine, Yasushi; Nukaya, Daiki; Iwata, Miki; Kishino, Akiyoshi; Takahashi, Masayo; Sasai, Yoshiki; Kimura, Toru |
| Source: |
Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322 |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2019 |
| Description: |
A three-dimensional retinal tissue (3D-retina) is a promising graft source for retinal transplantation therapy. We previously demonstrated that embryonic stem cells (ESCs) can generate 3D-retina in vitro using a self-organizing stem cell culture technique known as SFEBq. Here we show an optimized culture method for 3D-retina generation from feeder-free human pluripotent stem cells (hPSCs). Although feeder-free hPSC-maintenance culture was suitable for cell therapy, feeder-free hPSC-derived aggregates tended to collapse during 3D-differentiation culture. We found that the initial hPSC state was a key factor and that preconditioning of the hPSC state by modulating TGF-beta and Shh signaling improved self-formation of 3D-neuroepithelium. Using the preconditioning method, several feeder-free hPSC lines robustly differentiated into 3D-retina. In addition, changing preconditioning stimuli in undifferentiated hPSCs altered the proportions of neural retina and retinal pigment epithelium, important quality factors for 3D-retina. We demonstrated that the feeder-free hiPSC-derived 3D-retina differentiated into rod and cone photoreceptors in vitro and in vivo . Thus, preconditioning is a useful culture methodology for cell therapy to direct the initial hPSC state toward self-organizing 3D-neuroepithelium. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41598-019-55130-w |
| Availability: |
https://doi.org/10.1038/s41598-019-55130-w; https://www.nature.com/articles/s41598-019-55130-w.pdf; https://www.nature.com/articles/s41598-019-55130-w |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.FD12051E |
| Database: |
BASE |