Organoid technology has been widely adopted for drug discovery, where it offers more physiologically relevant pharmacology data than traditional two-dimensional (2D) cell models and can reduce or potentially replace animal testing. This article provides a brief overview of organoid technology, including its advantages and applications, before noting some key challenges and ways in which these are being overcome.
Organoids are complex three-dimensional (3D) in vitro cell cultures that mimic the architecture and functionality of in vivo tissues and organs. They are derived from embryonic stem cells (ESC), induced pluripotent stem cells (iPSC), or adult stem cells (ASC) that have been isolated from primary tissues. When working with organoids, it is critical that the culture medium contains all of the necessary components for the type of stem cells being used and the form of differentiation to be achieved, especially different cytokine and growth factor combinations. Examples include Noggin, R-spondin-1, EGF, BMP, and Wnt3a, which are essential in organoid formation. Over the past decade, organoid technology has developed to such an extent that it is now possible to model tissues from all three primary cell lineages (endoderm, mesoderm, and ectoderm). Organoids with key physiological structures and functions of the lung, mammary gland, and prostate have been reported, as well as organoids that recapitulate the pancreas, liver, gut, stomach, and other organs.
Organoid technology offers many advantages over traditional 2D cell culture and animal models. For example, establishing and maintaining an organoid system is much easier than working with zebrafish, mouse, or patient-derived xenograft (PDX) models. In addition, organoids can recapitulate human physiology far better than 2D cell cultures, C. elegans, or D. melanogaster. Other advantages of organoids include their close replication of developmental biology, their suitability for long-term experiments, and their capacity for genetic manipulation. Organoids also allow for genome-wide screening and are relatively inexpensive compared to some of the more advanced animal systems. Importantly, the use of organoids represents a viable alternative to animal testing that can create a new path to personalized medicine through the use of stem cells.
Organoid technology is being investigated for its utility to support many different applications. These range from fundamental research and disease modeling through to the development of cell-based therapies and personalized medicines. An important application of organoid technology involves modeling human diseases caused by mutations. By using gene-editing techniques such as CRISPR-Cas9, researchers can investigate diseases associated with different genetic defects. Organoid technology has also seen significant uptake for drug screening and development. Not only do organoids provide more realistic models than 2D cell cultures to identify and confirm new drug targets, but they also allow for generating pharmacology and toxicology data earlier in the drug development pipeline, which can mean stronger translation of results to a clinical setting.
While the benefits of organoid technology are widely recognized, several challenges remain to be addressed. First, organoids lack the microenvironment of connective tissue, vasculature, and immune cells compared to normal human tissues and organs, although this is being overcome by co-culturing with endothelial and immune cells, which provides a near physiological way of increasing nutrient exchange. Second, the slow maturation of organoids represents a critical limiting factor in modeling later-stage disease. Here, pre-treating organoids with various small molecules offers a solution. Other challenges center on establishing ecto, meso, and endoderm tissue interactions during organoid development and improving co-culture systems to study functional and spatio-temporal interactions in diverse cell populations.
Organoid research relies on a wide range of tools and techniques to culture, manipulate, and characterize these increasingly complex multicellular model systems. Premium quality growth factors and cytokines are essential for maintaining stem cell pluripotency, promoting differentiation when needed, and participating in signaling pathways for organoid formation, while well-validated antibodies are required for accurately detecting tissue-specific biomarkers via techniques such as western blotting, immunohistochemistry (IHC), and flow cytometry. Additionally, ELISA kits are necessary to measure protein biomarkers and cytokines, while qRT-PCR primers and cDNA clones respectively allow for disease- or tissue-specific screening and genome editing of somatic cells.
Sino Biological offers a comprehensive selection of products and services for organoid research, including over 800 recombinant cytokines covering the major families used in stem cell and various types of organoid culture. These are characterized by validated bioactivity, batch-to-batch consistency, and purity, and have been cited in high-impact publications. Additionally, an extensive collection of organoid marker antibodies used for multiple applications supports organoid validation and research.
To learn more about Sino Biological’s range of products and services for organoid research, visit sinobiological.com