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      Landscape of human organoids: Ideal model in clinics and research

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          Abstract

          In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

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          Public summary

          • The landscape of organoids history: organoids mark a new and efficient model in tissue and organ level.

          • Multiple applications of organoids in biomedicine and life healthcare.

          • Organoids benefit to drug discovery, disease study, prevention, control, and therapy.

          • Synthetic biology, artificial intelligence and automation integration broaden the role of organoids.

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          Most cited references246

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

            Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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              Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

              The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We have recently demonstrated the presence of about six cycling Lgr5(+) stem cells at the bottoms of small-intestinal crypts. Here we describe the establishment of long-term culture conditions under which single crypts undergo multiple crypt fission events, while simultanously generating villus-like epithelial domains in which all differentiated cell types are present. Single sorted Lgr5(+) stem cells can also initiate these cryptvillus organoids. Tracing experiments indicate that the Lgr5(+) stem-cell hierarchy is maintained in organoids. We conclude that intestinal cryptvillus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.
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                Author and article information

                Contributors
                Journal
                Innovation (Camb)
                Innovation (Camb)
                The Innovation
                Elsevier
                2666-6758
                01 April 2024
                06 May 2024
                01 April 2024
                : 5
                : 3
                : 100620
                Affiliations
                [1 ]Organ Regeneration X Lab, Lisheng East China Institute of Biotechnology, Peking University, Jiangsu 226200, China
                [2 ]Shanghai Lisheng Biotech, Shanghai 200092, China
                [3 ]LongHua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Xuhui District, Shanghai 200032, China
                [4 ]Department of Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
                [5 ]Department of Neurosurgery, Third Affiliated Hospital, Naval Medical University, Shanghai 200438, China
                [6 ]Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Academy of Forensic Science, Ministry of Justice, Shanghai 200063, China
                [7 ]Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
                [8 ]Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR 999078, China
                [9 ]CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
                [10 ]Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai 200032, China
                Author notes
                []Corresponding author xxhan@ 123456sibs.ac.cn
                [∗∗ ]Corresponding author cxdeng@ 123456um.edu.mo
                [∗∗∗ ]Corresponding author hexiao@ 123456ihep.ac.cn
                [∗∗∗∗ ]Corresponding author caox@ 123456fudan.edu.cn
                [11]

                These authors contributed equally

                Article
                S2666-6758(24)00058-4 100620
                10.1016/j.xinn.2024.100620
                11066475
                38706954
                6366bb08-17f0-45e5-a803-db09915d1ddf
                © 2024.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 31 October 2023
                : 29 March 2024
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                Review

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