Preconditioning the Initial State of Feeder-free Human Pluripotent Stem Cells Promotes Self-formation of Three-dimensional Retinal Tissue
| Autor: | Suguru Yamasaki, Yoshiki Sasai, Akiyoshi Kishino, Masayo Fujiwara, Masayo Takahashi, Michiko Mandai, Miki Iwata, Daiki Nukaya, Yoriko Hori, Atsushi Kuwahara, Keizo Matsushita, Toru Kimura, Kenji Watari, Yasushi Hiramine |
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| Rok vydání: | 2019 |
| Předmět: |
Retina
Multidisciplinary Retinal pigment epithelium Chemistry lcsh:R lcsh:Medicine Stem-cell differentiation Retinal Embryonic stem cell Article Stem-cell biotechnology Cell biology Neuroepithelial cell Cell therapy Transplantation chemistry.chemical_compound medicine.anatomical_structure embryonic structures Regenerative medicine medicine lcsh:Q sense organs lcsh:Science Induced pluripotent stem cell |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-55130-w |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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