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

Autor: Park S; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea., Kwon O; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Lee H; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea., Cho Y; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea., Yeun J; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea., Yoon SH; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea., Sun SY; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea., Huh Y; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Yu WD; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Park S; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Son N; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Jeon S; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea., Lee S; Digital Biotech Innovation Center, KRIBB, Daejeon, Republic of Korea., Kim DS; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea.; Digital Biotech Innovation Center, KRIBB, Daejeon, Republic of Korea., Lee SY; Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea., Son JG; Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea., Lee KJ; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam, Republic of Korea., Kim YI; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam, Republic of Korea., Lim JH; Department of Surgery, Gangnam Severance Hospital, Pancreatobiliary Cancer Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea., Yoo J; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam, Republic of Korea.; Organoid Standards Initiative (OSI), Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Republic of Korea.; CHA Organoid Research Center, CHA University, Seongnam, Republic of Korea., Lee TG; Nanobio Measurement Group, Division of Biomedical Metrology, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea., Son MY; Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea. myson@kribb.re.kr.; KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea. myson@kribb.re.kr.; Organoid Standards Initiative (OSI), Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Republic of Korea. myson@kribb.re.kr.; School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea. myson@kribb.re.kr., Im SG; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea. sgim@kaist.ac.kr.; KAIST Stem Cell Center, Department of Chemical and Biomolecular Engineering, Graduate School of Stem Cell & Regenerative Biology, KAIST, Daejeon, Republic of Korea. sgim@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Dec 02; Vol. 15 (1), pp. 10492. Date of Electronic Publication: 2024 Dec 02.
DOI: 10.1038/s41467-024-54653-9
Abstrakt: 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 (ISCs 3D-hIO ). XF-DISC enables remarkable expandability, exhibiting a 24-fold increase in cell numbers within 30 days, with long-term maintenance of ISCs 3D-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 ISCs 3D-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 ISC 3D-hIO culture method, XF-DISC is highly promising for the development of regenerative ISC therapy for human intestinal diseases.
Competing Interests: Competing interests: The authors declare no competing interests. Ethical considerations of working with human cells and animals: This study complies with all relevant ethical regulations. All studies based on human pluripotent stem cells were approved by the Korean Public IRB (IRB number: P01-201409-ES-01-09, P01-201609-31-002). Male NIG mice (Nod/scid-IL2Rgem1/GH, 6–12 weeks old; GHBio, Daejeon, Korea) were housed in a specific pathogen-free facility with a controlled 12-hour light/dark cycle, temperature maintained at 20-22 °C, and relative humidity at 55 ± 5%. The mice were provided with ad libitum access to water and fed a purified AIN-76A diet (Teklad Custom Research Diet, CA.170481; Envigo, Indianapolis, IN, USA). All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of KRIBB (KRIBB-AEC-22233). For the study based on human blood, informed consent was obtained prior to participation with approval from the IRB at Yonsei University Health System (IRB No. 3-2023-0347).
(© 2024. The Author(s).)
Databáze: MEDLINE
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