Stem Cell-Derived Organoids
1Emory University, Atlanta, USA
2Zhejiang University, Hangzhou, China
3Shenzhen Wingor Bio-technology Co. Ltd, Shenzhen, China
Stem Cell-Derived Organoids
Description
In the past few decades, conventional two-dimensional (2D) culture and animal models such as Drosophila, Zebrafish, and mammals – particularly the mouse – have been instrumental to gain insight into the developmental and pathophysiological mechanisms behind human genetic disorders/diseases. However, the lack of spatial information and discrepancy in genetics and physiology between animal models and humans hinders the translatability of research outcomes into clinical applications, particularly for some chronic, complex, and intractable diseases. For example, clinical trials using mGluR5 antagonists that were informed by studies on animal models for human fragile X syndrome (FXS) have generated disappointing results.
To overcome the limitations of the existing 2-D cultures and animal models, studies with organoids have gained extensive attention. Organoids are essentially a miniaturized and simplified version of an organ generated in vitro with conserved in vivo microanatomy. This in vitro 3D culture, starting from human embryonic stem cells (hESC) or human induced pluripotency stem cells (hiPSC), are faithfully parallel to human organogenesis in a way that recapitulates many aspects of human organ development. As such, organoids have enabled researchers to develop human tissues or organs that can be used as an invaluable platform for biomedical study, pathological investigation of human genetic disorders/diseases, drug screening and development for therapeutic strategies, as well as regeneration medicine in a dish, otherwise inaccessible to experimentation.
Thus far, various types of organoids have been generated, such as frontal brain, cerebral cortex, cortical brain, optic cup, lung, intestine, stomach, pituitary, colon, liver, gastric, pancreatic, thyroid, renal, bone spheroids, fallopian tube, endometrial, bladder, saliva gland, mammary, retinal, inner-ear, prostate, oesophagus, and kidney. Despite these early breakthroughs in 3D culture systems, multiple engineering and conceptual challenges have limited the efficiency and quality of the organoids in recapitulating the development of human organs, which are essential for a therapeutic perspective. The leading technical limitations found in the in vitro culture system have been lack of vascularization, cellular diversity, insufficiency, and undermined tissue maturity. Excitingly, a technical breakthrough has been made in the formation of networks of functional vascular-like vessels in human cortical organoids (hCOs) via the induced expression of human ETS variant 2 (ETV2). The vascularized hCOs (vhCOs) mimic cortical features more precisely, such as organization, less hypoxia and apoptosis, shedding light on the generation of organoids in the direction of higher efficiency and mirroring human organogenesis.
These achievements have been inspiring scientists to switch their focus from animal models to human- approaching models to investigate the pathological mechanisms more precisely for human genetic disorders/diseases. Thus, it is of importance to launch a Special Issue with special emphasis on advances in the generation and application of stem cells-derived organoids. We invite original research or review articles dealing with stem cells, organoids generation, and applications to biomedical study.
Potential topics include but are not limited to the following:
- Technical improvements on the quality and generation efficiency of a variety of organoids, representing the main human organs such as the optic cup, intestine, stomach, pituitary, colon, liver, gastric, pancreatic, thyroid, renal, bone spheroids, fallopian tube, endometrial, bladder, saliva gland, mammary, retinal, inner-ear, prostate, esophagus, and lung organoids
- Generation of human brain organoids, such as frontal brain, cerebral cortex, cortical brain, and their applications in modelling human brain development and human neurological disorders/diseases
- Generation of cancer-derived organoids and their applications in modelling cancers such as stomach, colon, liver, pancreatic, renal, endometrial, mammary, retinal, bladder, oesophagus, prostate and lung cancers, and their application in pathological study and therapy
- Generation of organoids and their applications in modelling immune / infectious diseases
- Oraganoids in modelling congenital diseases such as cystic fibrosis (CF), autism spectrum disorder (ASD), primary microcephaly, Leber congenital amaurosis, AD, PD, motor neuron diseases, and frontotemporal dementia
- Gene editing in organoids
- Epigenetic study using organoids
- Organoid-based drug screening for dissection of pathological pathways and therapeutic applications