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Generation of 3D lacrimal gland organoids from human pluripotent stem cells

Ryuhei Hayashi (), Toru Okubo, Yuji Kudo, Yuki Ishikawa, Tsutomu Imaizumi, Kenji Suzuki, Shun Shibata, Tomohiko Katayama, Sung-Joon Park, Robert D. Young, Andrew J. Quantock and Kohji Nishida
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Ryuhei Hayashi: Osaka University Graduate School of Medicine
Toru Okubo: Osaka University Graduate School of Medicine
Yuji Kudo: Osaka University Graduate School of Medicine
Yuki Ishikawa: Osaka University Graduate School of Medicine
Tsutomu Imaizumi: Osaka University Graduate School of Medicine
Kenji Suzuki: Osaka University Graduate School of Medicine
Shun Shibata: Osaka University Graduate School of Medicine
Tomohiko Katayama: Osaka University Graduate School of Medicine
Sung-Joon Park: University of Tokyo
Robert D. Young: Cardiff University
Andrew J. Quantock: Cardiff University
Kohji Nishida: Osaka University Graduate School of Medicine

Nature, 2022, vol. 605, issue 7908, 126-131

Abstract: Abstract Lacrimal glands are the main exocrine glands of the eyes. Situated within the orbit, behind the upper eyelid and towards the temporal side of each eye, they secrete lacrimal fluid as a major component of the tear film. Here we identify cells with characteristics of lacrimal gland primordia that emerge in two-dimensional eye-like organoids cultured from human pluripotent stem cells1. When isolated by cell sorting and grown under defined conditions, the cells form a three-dimensional lacrimal-gland-like tissue organoid with ducts and acini, enabled by budding and branching. Clonal colony analyses indicate that the organoids originate from multipotent ocular surface epithelial stem cells. The organoids exhibit notable similarities to native lacrimal glands on the basis of their morphology, immunolabelling characteristics and gene expression patterns, and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.

Date: 2022
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DOI: 10.1038/s41586-022-04613-4

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