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Human organoid models and their role in medical research

organoids

organoids

 

Human organoids are in vitro 3D biological structures that recapitulate the key function of an in vivo organ. They are amenable to any experimental approach that has been developed for cell lines and patient-derived animal models, thereby complementing the existing model systems in biological and medical research. 

Furthermore, the analysis of organoid formation during the model development can provide valuable information about the mechanisms in organ regeneration, highlighting their potential application in drug testing and molecular medicine

 

Methods to obtain organoids

Organoids with limited or complete biological functions can be made for almost all body organs. There are published data available for the kidney, liver, pancreas, gastrointestinal tract, mammary glands, upper and lower lungs, prostate, thyroid, retina and brain. These organoids can be derived either from adult stem cells (ASCs), which can be directly sourced from the biopsy samples, or pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) or induced PSCs (iPSCs) through reprogramming differentiated cell types. Organoids derived from ASCs exploit the tissue regeneration process that is driven by the organ cells and can be established directly from the healthy or diseased epithelium of many organs.

 

Organoids from ASCs: 

In the ASC-derived organoid system, single stem cells or clusters of cells are usually seeded into a biological matrix that mimics essential biochemical aspects of the organ. Under appropriate signalling conditions that involve key regulatory pathways, these cells undergo proliferation, differentiation, migration and selection. Despite the lack of spatially organized cues, they grow into symmetrical structures and acquire remarkable architectural complexity that mirrors the organization and cell type diversity of its in vivo organ counterpart. 

 

Organoids from PSCs:

Similar to the development of organs in vivo, the PSCs can proliferate, differentiate and eventually form organoids with structural and functional resemblance to the adult organ. For example, the generation of brain organoids usually starts with aggregates of PSCs, that form embryoid bodies that are embedded in an extracellular protein-rich matrix (ECM). The cells in the ECM grow in a self-organized manner to form neuroepithelial structures with compartments that correspond to multiple brain regions. 

 

PSC-derived organoids are promising research platforms for creating models for organs for which tissue samples cannot be easily obtained, such as the brain. They can also be used for modelling the overall developmental processes that occur during organogenesis.

 

Applications of organoids

 

Limitations of organoid systems

Cell maturity and function

 

Accessibility and removing contaminants

 

Heterogeneity of the organoid model

 

Validation of the organoid system

 

Perspectives

 

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Sources

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