-
American Journal of Physiology. Cell... Jul 2020In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in... (Review)
Review
In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in the past, the lack of tissue architecture and complexity of such model fails to inform the true biological processes in vivo. Recent advances in the organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of the primary tissues. Such organoid technology enables researchers to recreate human organs and diseases in a dish and thus holds great promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. In this review, we provide an overview of the organoid history and development. We discuss the strengths and limitations of organoids as well as their potential applications in the laboratory and the clinic.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Humans; Models, Biological; Organ Culture Techniques; Organoids
PubMed: 32459504
DOI: 10.1152/ajpcell.00120.2020 -
Journal of Molecular Medicine (Berlin,... Apr 2021Organoid technology has rapidly transformed basic biomedical research and contributed to significant discoveries in the last decade. With the application of protocols to... (Review)
Review
Organoid technology has rapidly transformed basic biomedical research and contributed to significant discoveries in the last decade. With the application of protocols to generate organoids from cancer tissue, organoid technology has opened up new opportunities for cancer research and therapy. Using organoid cultures derived from healthy tissues, different aspects of tumour initiation and progression are widely studied including the role of pathogens or specific cancer genes. Cancer organoid cultures, on the other hand, are applied to generate biobanks, perform drug screens, and study mutational signatures. With the incorporation of cellular components of the tumour microenvironment such as immune cells into the organoid cultures, the technology is now also exploited in the rapidly advancing field of immuno-oncology. In this review, I discuss how organoid technology is currently being utilised in cancer research and what obstacles are still to be overcome for its broader use in anti-cancer therapy.
Topics: Biological Specimen Banks; Carcinogenesis; Cell Transformation, Neoplastic; DNA Mutational Analysis; Drug Screening Assays, Antitumor; Epithelial Cells; Forecasting; Genes, Neoplasm; Humans; Medical Oncology; Neoplasm Metastasis; Neoplasms; Neoplastic Stem Cells; Organoids; Stem Cell Research; Translational Research, Biomedical; Tumor Microenvironment
PubMed: 33057820
DOI: 10.1007/s00109-020-01990-z -
Signal Transduction and Targeted Therapy May 2022Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived... (Review)
Review
Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived from healthy individuals or patients that recapitulate the cellular heterogeneity, structure, and functions of human organs. The advent of human 3D organoid systems is now possible to allow remarkably detailed observation of stem cell morphogens, maintenance and differentiation resemble primary tissues, enhancing the potential to study both human physiology and developmental stage. As they are similar to their original organs and carry human genetic information, organoids derived from patient hold great promise for biomedical research and preclinical drug testing and is currently used for personalized, regenerative medicine, gene repair and transplantation therapy. In recent decades, researchers have succeeded in generating various types of organoids mimicking in vivo organs. Herein, we provide an update on current in vitro differentiation technologies of brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized and multi-lineage organoids, discuss the differences between PSC- and AdSC-derived organoids, summarize the potential applications of stem cell-derived organoids systems in the laboratory and clinic, and outline the current challenges for the application of organoids, which would deepen the understanding of mechanisms of human development and enhance further utility of organoids in basic research and clinical studies.
Topics: Adult; Adult Stem Cells; Cell Differentiation; Humans; Organoids; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 35610212
DOI: 10.1038/s41392-022-01024-9 -
Science (New York, N.Y.) Jan 2022Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational...
Epithelial organoids are stem cell–derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.
Topics: Animals; Cell Differentiation; Cell Shape; Epithelial Cells; Hydrogels; Intestinal Mucosa; Mice; Organogenesis; Organoids; Paneth Cells; Receptors, Notch; Signal Transduction; Stem Cells; Tissue Culture Techniques; Tissue Engineering; YAP-Signaling Proteins
PubMed: 34990240
DOI: 10.1126/science.aaw9021 -
Advanced Materials (Deerfield Beach,... Nov 2021Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional... (Review)
Review
Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional characteristics of native organs. Current organoid technologies have been striding toward identifying the essential factors for controlling the processes involved in organoid development, including physical cues and biochemical signaling. There is a growing demand for engineering dynamic niches characterized by conditions that resemble in vivo organogenesis to generate reproducible and reliable organoids for various applications. Innovative biomaterial-based and advanced engineering-based approaches have been incorporated into conventional organoid culture methods to facilitate the development of organoid research. The recent advances in organoid engineering, including extracellular matrices and genetic modulation, are comprehensively summarized to pinpoint the parameters critical for organ-specific patterning. Moreover, perspective trends in developing tunable organoids in response to exogenous and endogenous cues are discussed for next-generation developmental studies, disease modeling, and therapeutics.
Topics: Biocompatible Materials; Biomedical Engineering; Cell Culture Techniques, Three Dimensional; Extracellular Matrix; Genetic Engineering; Humans; Hydrogels; Neoplasms; Organoids; Stem Cells
PubMed: 34561899
DOI: 10.1002/adma.202007949 -
Cell Sep 2020Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive...
Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Line; Electrophysiology; Female; Gene Expression Regulation, Developmental; Genetic Predisposition to Disease; Humans; In Situ Hybridization; Induced Pluripotent Stem Cells; Microscopy, Electron; Multigene Family; Naphthoquinones; Organoids; Retina; Single-Cell Analysis; Synapses; Transcriptome
PubMed: 32946783
DOI: 10.1016/j.cell.2020.08.013 -
Gut Dec 2019Organoid cultures have emerged as an alternative in vitro system to recapitulate tissues in a dish. While mouse models and cell lines have furthered our understanding of... (Review)
Review
Organoid cultures have emerged as an alternative in vitro system to recapitulate tissues in a dish. While mouse models and cell lines have furthered our understanding of liver biology and associated diseases, they suffer in replicating key aspects of human liver tissue, in particular its complex architecture and metabolic functions. Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. These represent a promising addition to our toolbox to gain a deeper understanding of this complex organ. In this perspective we will review the advances in the liver organoid field, its limitations and potential for biomedical applications.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Cell Line; Humans; Liver; Models, Biological; Organoids; Regenerative Medicine
PubMed: 31300517
DOI: 10.1136/gutjnl-2019-319256 -
Journal of Hematology & Oncology May 2022Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These... (Review)
Review
Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.
Topics: Cell Culture Techniques; Humans; Neoplasms; Organoids; Precision Medicine; Tumor Microenvironment
PubMed: 35551634
DOI: 10.1186/s13045-022-01278-4 -
Cell Stem Cell May 2021Hepatic, pancreatic, and biliary (HPB) organoids are powerful tools for studying development, disease, and regeneration. As organoid research expands, the need for clear... (Review)
Review
Hepatic, pancreatic, and biliary (HPB) organoids are powerful tools for studying development, disease, and regeneration. As organoid research expands, the need for clear definitions and nomenclature describing these systems also grows. To facilitate scientific communication and consistent interpretation, we revisit the concept of an organoid and introduce an intuitive classification system and nomenclature for describing these 3D structures through the consensus of experts in the field. To promote the standardization and validation of HPB organoids, we propose guidelines for establishing, characterizing, and benchmarking future systems. Finally, we address some of the major challenges to the clinical application of organoids.
Topics: Consensus; Liver; Organoids; Pancreas
PubMed: 33961769
DOI: 10.1016/j.stem.2021.04.005 -
Cell Metabolism Aug 2019Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different...
Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different healthy and diseased pluripotent stem cell lines, we developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic resemblance to in vivo-derived tissues. Under free fatty acid treatment, organoids, but not reaggregated cocultured spheroids, recapitulated key features of steatohepatitis, including steatosis, inflammation, and fibrosis phenotypes in a successive manner. Interestingly, an organoid-level biophysical readout with atomic force microscopy demonstrated that organoid stiffening reflects the fibrosis severity. Furthermore, organoids from patients with genetic dysfunction of lysosomal acid lipase phenocopied severe steatohepatitis, rescued by FXR agonism-mediated reactive oxygen species suppression. The presented key methodology and preliminary results offer a new approach for studying a personalized basis for inflammation and fibrosis in humans, thus facilitating the discovery of effective treatments.
Topics: Cells, Cultured; Fatty Liver; Humans; Male; Models, Biological; Organoids; Pluripotent Stem Cells
PubMed: 31155493
DOI: 10.1016/j.cmet.2019.05.007