{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:12:02Z","timestamp":1789683122284,"version":"4.0.1"},"reference-count":119,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K16232"],"award-info":[{"award-number":["18K16232"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21J01689"],"award-info":[{"award-number":["21J01689"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labor and Welfare","award":["not available (Grants-in-Aid for Scientific Research on Hypothalamo-hypophyseal Disorders and Grants-in-Aid for Scientific Research on Endocrine Syndrome with Sexual Differentiation and Maturation)"],"award-info":[{"award-number":["not available (Grants-in-Aid for Scientific Research on Hypothalamo-hypophyseal Disorders and Grants-in-Aid for Scientific Research on Endocrine Syndrome with Sexual Differentiation and Maturation)"]}]},{"name":"Center for iPS Cell Research and Application","award":["not available (Fellowship Program of Development of Young Researchers)"],"award-info":[{"award-number":["not available (Fellowship Program of Development of Young Researchers)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human pluripotent stem cells (hPSCs) are grouped into two cell types; embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). hESCs have provided multiple powerful platforms to study human biology, including human development and diseases; however, there were difficulties in the establishment of hESCs from human embryo and concerns over its ethical issues. The discovery of hiPSCs has expanded to various applications in no time because hiPSCs had already overcome these problems. Many hPSC-based studies have been performed using two-dimensional monocellular culture methods at the cellular level. However, in many physiological and pathophysiological conditions, intra- and inter-organ interactions play an essential role, which has hampered the establishment of an appropriate study model. Therefore, the application of recently developed technologies, such as three-dimensional organoids, bioengineering, and organ-on-a-chip technology, has great potential for constructing multicellular tissues, generating the functional organs from hPSCs, and recapitulating complex tissue functions for better biological research and disease modeling. Moreover, emerging techniques, such as single-cell transcriptomics, spatial transcriptomics, and artificial intelligence (AI) allowed for a denser and more precise analysis of such heterogeneous and complex tissues. Here, we review the applications of hPSCs to construct complex organs and discuss further prospects of disease modeling and drug discovery based on these PSC-derived organs.<\/jats:p>","DOI":"10.3390\/ijms221910184","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T22:24:13Z","timestamp":1632695053000},"page":"10184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques"],"prefix":"10.3390","volume":"22","author":[{"given":"Ryusaku","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"},{"name":"Department of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan"},{"name":"Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan"},{"name":"Medical-Risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Tokyo 103-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"},{"name":"Department of Diabetes and Endocrinology, Nara Medical University, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e27041","DOI":"10.7554\/eLife.27041","article-title":"The Human Cell Atlas","volume":"6","author":"Regev","year":"2017","journal-title":"eLife"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.stem.2016.02.011","article-title":"Complex Tissue and Disease Modeling using hiPSCs","volume":"18","author":"Passier","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10821","article-title":"Probing sporadic and 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