Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy

Seonghyeon Park, Ohman Kwon, Hana Lee, Younghak Cho, Jemin Yeun, Sung Hyun Yoon, Sang Yu Sun, Yubin Huh, Won Dong Yu, Sohee Park, Naeun Son, Sojeong Jeon, Sugi Lee, Dae-Soo Kim, Sun Young Lee, Jin Gyeong Son, Kyung Jin Lee, Yong Il Kim, Jin Hong Lim, Jongman Yoo, Tae Geol Lee, Mi-Young Son () and Sung Gap Im ()
Additional contact information
Seonghyeon Park: 291 Daehak-ro
Ohman Kwon: 125 Gwahak-ro
Hana Lee: 125 Gwahak-ro
Younghak Cho: 291 Daehak-ro
Jemin Yeun: 291 Daehak-ro
Sung Hyun Yoon: 291 Daehak-ro
Sang Yu Sun: 291 Daehak-ro
Yubin Huh: 125 Gwahak-ro
Won Dong Yu: 125 Gwahak-ro
Sohee Park: 125 Gwahak-ro
Naeun Son: 125 Gwahak-ro
Sojeong Jeon: 125 Gwahak-ro
Sugi Lee: KRIBB
Dae-Soo Kim: Korea University of Science and Technology (UST)
Sun Young Lee: 267 Gajeong-ro
Jin Gyeong Son: 267 Gajeong-ro
Kyung Jin Lee: ORGANOIDSCIENCES Ltd.
Yong Il Kim: ORGANOIDSCIENCES Ltd.
Jin Hong Lim: Yonsei University College of Medicine
Jongman Yoo: ORGANOIDSCIENCES Ltd.
Tae Geol Lee: 267 Gajeong-ro
Mi-Young Son: 125 Gwahak-ro
Sung Gap Im: 291 Daehak-ro

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The need for basement membrane extract (BME) with undefined constituents, such as Matrigel, for intestinal stem cell (ISC) culture in traditional systems poses a significant barrier that must be overcome for the development of clinical-grade, scalable, ready-to-use ISCs. Here, we propose a functional polymer-based xenogeneic-free dish for the culture of intestinal stem cells (XF-DISC), ensuring substantially prolonged maintenance of ISCs derived from 3-dimensional human intestinal organoids (ISCs3D-hIO). XF-DISC enables remarkable expandability, exhibiting a 24-fold increase in cell numbers within 30 days, with long-term maintenance of ISCs3D-hIO for more than 30 consecutive passages (>210 days). In addition, XF-DISC is fully compatible with a cell banking system. Notably, human pluripotent stem cell-derived ISCs3D-hIO cultured on XF-DISC are successfully transplanted into intestinal injury and inflammation mouse models, leading to engraftment and regeneration of damaged mouse intestinal epithelium. As a reliable and scalable xenogeneic-free ISC3D-hIO culture method, XF-DISC is highly promising for the development of regenerative ISC therapy for human intestinal diseases.

Date: 2024
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DOI: 10.1038/s41467-024-54653-9

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