Human intestinal organoid-derived PDGFRα + mesenchymal stroma enables proliferation and maintenance of LGR4 + epithelial stem cells.

"Declarations Ethics approval and consent to participateAll experiments involving handling of human cells and tissues were approved by the Institutional Review Board at the National Center for Child Health and Development (2021–178). In compliance with the Declaration of Helsinki, informed consent was obtained from all tissues and cell donors. When the donors were under 18, informed consent was obtained from parents. Human cells in this study were utilized in full compliance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects (Ministry of Health, Labor, and Welfare (MHLW), Japan; Ministry of Education, Culture, Sports, Science and Technology (MEXT, Japan) and performed in full compliance with the Ethical Guidelines for Clinical Studies (Ministry of Health, Labor, and Welfare, Japan). The cells were banked after approval of the Institutional Review Board at the National Institute of Biomedical Innovation (May 9, 2006). The derivation and cultivation of human embryonic stem cell (hESC) lines were performed in full compliance with “the Guidelines for Derivation and Distribution of Human Embryonic Stem Cells (Notification of MEXT, No. 156 of August 21, 2009; Notification of MEXT, No. 86 of May 20, 2010) and “the Guidelines for Utilization of Human Embryonic Stem Cells (Notification of MEXT, No. 157 of August 21, 2009; Notification of MEXT, No. 87 of May 20, 2010)”. All procedures of animal experiments were approved by the Institutional Animal Care and Use Committee in National Center for Child Health and Development, based on the basic guidelines for the conduct of animal experiments in implementing agencies under the jurisdiction of the Ministry of Health, Labor and Welfare (Notification of MHLW, No. 0220–1 of February 20, 2015). The Institutional Animal Care and Use Committee of the National Center for Child Health and Development approved the protocols of the animal experiments (approval number: A2003-002-C20-M01, title: Research on regenerative medicine and cell medicine using mesenchymal stem cells, iPS cells, and ES cells, and on toxicity testing). Animal experiments were performed according to protocols approved by the Institutional Animal Care and Use Committee of the National Research Institute for Child Health and Development. Consent for publicationNot applicable. Competing interestsAU is an Associate Editor of the journal, but he was not involved in the peer review process or the decision-making of this article. AU and CJ are co-researchers with Dai Nippon Printing Ltd. AU is a stockholder of iHaes. The other authors declare that there is no conflict of interest regarding the work described herein. Competing interests AU is an Associate Editor of the journal, but he was not involved in the peer review process or the decision-making of this article. AU and CJ are co-researchers with Dai Nippon Printing Ltd. AU is a stockholder of iHaes. The other authors declare that there is no conflict of interest regarding the work described herein."

"Funding This research was supported by AMED; by KAKENHI; by the Grant of National Center for Child Health and Development; by JST, the establishment of university fellowships toward the creation of science technology innovation, Grant Number JPMJFS2102. The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript."