Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy
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...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54653-9 |
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| author | 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 Sung Gap Im |
| author_facet | 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 Sung Gap Im |
| author_sort | Seonghyeon Park |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7dffbdd44b554b0c96573fc7e5072265 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7dffbdd44b554b0c96573fc7e50722652025-08-20T02:20:38ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-54653-9Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapySeonghyeon Park0Ohman Kwon1Hana Lee2Younghak Cho3Jemin Yeun4Sung Hyun Yoon5Sang Yu Sun6Yubin Huh7Won Dong Yu8Sohee Park9Naeun Son10Sojeong Jeon11Sugi Lee12Dae-Soo Kim13Sun Young Lee14Jin Gyeong Son15Kyung Jin Lee16Yong Il Kim17Jin Hong Lim18Jongman Yoo19Tae Geol Lee20Mi-Young Son21Sung Gap Im22Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roDigital Biotech Innovation Center, KRIBBKRIBB School of Bioscience, Korea University of Science and Technology (UST)Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-roNanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-roR&D Institute, ORGANOIDSCIENCES Ltd.R&D Institute, ORGANOIDSCIENCES Ltd.Department of Surgery, Gangnam Severance Hospital, Pancreatobiliary Cancer Clinic, Yonsei University College of MedicineR&D Institute, ORGANOIDSCIENCES Ltd.Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-roStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-roDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-roAbstract 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.https://doi.org/10.1038/s41467-024-54653-9 |
| spellingShingle | 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 Sung Gap Im Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy Nature Communications |
| title | Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy |
| title_full | Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy |
| title_fullStr | Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy |
| title_full_unstemmed | Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy |
| title_short | Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy |
| title_sort | xenogeneic free culture of human intestinal stem cells on functional polymer coated substrates for scalable clinical grade stem cell therapy |
| url | https://doi.org/10.1038/s41467-024-54653-9 |
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