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Nature Reviews. Genetics Nov 2018Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns.... (Review)
Review
Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Humans; Models, Biological; Organoids; Stem Cells
PubMed: 30228295
DOI: 10.1038/s41576-018-0051-9 -
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 -
Science (New York, N.Y.) Jul 2014Classical experiments performed half a century ago demonstrated the immense self-organizing capacity of vertebrate cells. Even after complete dissociation, cells can... (Review)
Review
Classical experiments performed half a century ago demonstrated the immense self-organizing capacity of vertebrate cells. Even after complete dissociation, cells can reaggregate and reconstruct the original architecture of an organ. More recently, this outstanding feature was used to rebuild organ parts or even complete organs from tissue or embryonic stem cells. Such stem cell-derived three-dimensional cultures are called organoids. Because organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies. Here, we summarize this rapidly evolving field and outline the potential of organoid technology for future biomedical research.
Topics: Animals; Brain; Cell Culture Techniques; Disease; Drug Evaluation, Preclinical; Humans; Intestines; Liver; Mice; Models, Biological; Mutagenesis; Organ Culture Techniques; Organogenesis; Organoids; Pluripotent Stem Cells; Retina; Tissue Engineering
PubMed: 25035496
DOI: 10.1126/science.1247125 -
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 -
Journal of Molecular Cell Biology Aug 2020For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade... (Review)
Review
For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.
Topics: Animals; Humans; Models, Biological; Organ Specificity; Organoids; Pluripotent Stem Cells; Tissue Engineering
PubMed: 32249317
DOI: 10.1093/jmcb/mjaa012 -
Trends in Molecular Medicine May 2017Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature... (Review)
Review
Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature of original tissues. Thus, organoid technology has been rapidly applied to understanding stem cell biology, organogenesis, and various human pathologies. The recent development of human patient-derived organoids has enabled disease modeling with precision, highlighting their great potential in biomedical applications, translational medicine, and personalized therapy. In light of recent breakthroughs using organoids, it is only apt that we appreciate the advantages and shortcomings of this technology to exploit its full potential. We discuss recent advances in the application of organoids in studying cancer and hereditary diseases, as well as in the examination of host cell-microorganism interactions.
Topics: Animals; Disease Models, Animal; Humans; Neoplasms; Organoids; Pluripotent Stem Cells
PubMed: 28341301
DOI: 10.1016/j.molmed.2017.02.007 -
Clinical and Translational Medicine Dec 2023Despite enormous advances in the generation of organoids, robust and stable protocols of organoids are still a major challenge to researchers. Research for assessing... (Review)
Review
Despite enormous advances in the generation of organoids, robust and stable protocols of organoids are still a major challenge to researchers. Research for assessing structures of organoids and the evaluations of their functions on in vitro or in vivo is often limited by precision strategies. A growing interest in assessing organoids has arisen, aimed at standardizing the process of obtaining organoids to accurately resemble human-derived tissue. The complex microenvironment of organoids, intricate cellular crosstalk, organ-specific architectures and further complicate functions urgently quest for high-through schemes. By utilizing multi-omics analysis and single-cell analysis, cell-cell interaction mechanisms can be deciphered, and their structures can be investigated in a detailed view by histological analysis. In this review, we will conclude the novel approaches to study the molecular mechanism and cell heterogeneity of organoids and discuss the histological and morphological similarity of organoids in comparison to the human body. Future perspectives on functional analysis will be developed and the organoids will become mature models.
Topics: Humans; Organoids
PubMed: 38115706
DOI: 10.1002/ctm2.1499 -
Biological Psychiatry Apr 2023The past decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders, including Mendelian, de novo, and somatic factors. These... (Review)
Review
The past decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders, including Mendelian, de novo, and somatic factors. These discoveries provide opportunities to understand cellular and molecular mechanisms as well as potential gene-gene and gene-environment interactions to support novel therapies. Stem cell-based models, particularly human brain organoids, can capture disease-associated alleles in the context of the human genome, engineered to mirror disease-relevant aspects of cellular complexity and developmental timing. These models have brought key insights into neurodevelopmental disorders as diverse as microcephaly, autism, and focal epilepsy. However, intrinsic organoid-to-organoid variability, low levels of certain brain-resident cell types, and long culture times required to reach maturity can impede progress. Several recent advances incorporate specific morphogen gradients, mixtures of diverse brain cell types, and organoid engraftment into animal models. Together with nonhuman primate organoid comparisons, mechanisms of human neurodevelopmental disorders are emerging.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Brain; Neurodevelopmental Disorders; Autistic Disorder; Organoids
PubMed: 36759260
DOI: 10.1016/j.biopsych.2023.01.012 -
Nature Materials Feb 2021In recent years considerable progress has been made in the development of faithful procedures for the differentiation of human pluripotent stem cells (hPSCs). An... (Review)
Review
In recent years considerable progress has been made in the development of faithful procedures for the differentiation of human pluripotent stem cells (hPSCs). An important step in this direction has also been the derivation of organoids. This technology generally relies on traditional three-dimensional culture techniques that exploit cell-autonomous self-organization responses of hPSCs with minimal control over the external inputs supplied to the system. The convergence of stem cell biology and bioengineering offers the possibility to provide these stimuli in a controlled fashion, resulting in the development of naturally inspired approaches to overcome major limitations of this nascent technology. Based on the current developments, we emphasize the achievements and ongoing challenges of bringing together hPSC organoid differentiation, bioengineering and ethics. This Review underlines the need for providing engineering solutions to gain control of self-organization and functionality of hPSC-derived organoids. We expect that this knowledge will guide the community to generate higher-grade hPSC-derived organoids for further applications in developmental biology, drug screening, disease modelling and personalized medicine.
Topics: Bioengineering; Humans; Organoids; Pluripotent Stem Cells
PubMed: 33199860
DOI: 10.1038/s41563-020-00804-4 -
Nature Sep 2020Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology. However, the approaches that...
Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology. However, the approaches that are used at present to derive these organoids in three-dimensional matrices result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host-microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Cryptosporidium parvum; Homeostasis; Human Embryonic Stem Cells; Human Umbilical Vein Endothelial Cells; Humans; Intestines; Mice; Models, Biological; Morphogenesis; Organoids; Regeneration; Regenerative Medicine; Stem Cells; Tissue Culture Techniques; Tissue Engineering; Tissue Scaffolds
PubMed: 32939089
DOI: 10.1038/s41586-020-2724-8