Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

Luo, Juan

doi:10.1186/s13578-021-00617-1

Cited by 13 publications

(19 citation statements)

References 155 publications

(150 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An obvious advantage of organoid cultures for disease modeling, compared with traditional cell cultures of a single cell type, is their ability to mimic large quantities of pathologies by recapitulating specific human features that could be relevant for translational studies [ 191 ]. Brain organoids represent a powerful in vitro approach to model brain development [ 35 , 108 , 192 ], understand neurodevelopmental diseases [ 193 ], recapitulate aspects of neurodegenerative diseases [ 194 , 195 , 196 , 197 ], and for personalized drug screening when an individual’s hiPSCs are used [ 49 , 198 ]; while retinal organoids have been reported as human eye disease models, pharmaceutical testbeds, and cell sources for transplantations [ 5 , 82 , 84 , 98 , 100 , 199 , 200 ].…”

Section: Discussionmentioning

confidence: 99%

Brain and Retinal Organoids for Disease Modeling: The Importance of In Vitro Blood–Brain and Retinal Barriers Studies

Martinelli

Tayebati

Tomassoni

et al. 2022

Cells

View full text Add to dashboard Cite

Brain and retinal organoids are functional and dynamic in vitro three-dimensional (3D) structures derived from pluripotent stem cells that spontaneously organize themselves to their in vivo counterparts. Here, we review the main literature data of how these organoids have been developed through different protocols and how they have been technically analyzed. Moreover, this paper reviews recent advances in using organoids to model neurological and retinal diseases, considering their potential for translational applications but also pointing out their limitations. Since the blood–brain barrier (BBB) and blood–retinal barrier (BRB) are understood to play a fundamental role respectively in brain and eye functions, both in health and in disease, we provide an overview of the progress in the development techniques of in vitro models as reliable and predictive screening tools for BBB and BRB-penetrating compounds. Furthermore, we propose potential future directions for brain and retinal organoids, in which dedicated biobanks will represent a novel tool for neuroscience and ophthalmology research.

show abstract

Section: Discussionmentioning

confidence: 99%

Brain and Retinal Organoids for Disease Modeling: The Importance of In Vitro Blood–Brain and Retinal Barriers Studies

Martinelli

Tayebati

Tomassoni

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“… 45 In addition, analysis of the anatomical and functional components of assembloids in both normal and disease models can give a comprehensive understanding of scenarios in which CNS development goes awry as well as inspire novel treatment approaches. 76 , 110 …”

Section: Cns Assembloids: Assembled and Integrated Organoids With Imp...mentioning

confidence: 99%

“…These models give researchers the unique ability to explore interneuron migration and axon projection, two main phenotypic defects seen in both neurodevelopmental and neuropsychiatric disorders. 59 , 66 , 76 , 110 , 111 , 114 …”

Section: Cns Assembloids: Assembled and Integrated Organoids With Imp...mentioning

confidence: 99%

Human mini brains and spinal cords in a dish: Modeling strategies, current challenges, and prospective advances

et al. 2022

View full text Add to dashboard Cite

Engineered three-dimensional (3D) in vitro and ex vivo neural tissues, also known as “mini brains and spinal cords in a dish,” can be derived from different types of human stem cells via several differentiation protocols. In general, human mini brains are micro-scale physiological systems consisting of mixed populations of neural progenitor cells, glial cells, and neurons that may represent key features of human brain anatomy and function. To date, these specialized 3D tissue structures can be characterized into spheroids, organoids, assembloids, organ-on-a-chip and their various combinations based on generation procedures and cellular components. These 3D CNS models incorporate complex cell-cell interactions and play an essential role in bridging the gap between two-dimensional human neuroglial cultures and animal models. Indeed, they provide an innovative platform for disease modeling and therapeutic cell replacement, especially shedding light on the potential to realize personalized medicine for neurological disorders when combined with the revolutionary human induced pluripotent stem cell technology. In this review, we highlight human 3D CNS models developed from a variety of experimental strategies, emphasize their advances and remaining challenges, evaluate their state-of-the-art applications in recapitulating crucial phenotypic aspects of many CNS diseases, and discuss the role of contemporary technologies in the prospective improvement of their composition, consistency, complexity, and maturation.

show abstract

“…Another strategies in in vitro cell culture techniques increasingly seek to recapitulate complex tissue- and organ-level phenotypes, such as spheroid-based organoids, three-dimensional (3D) cell culture systems, and even microfluidic devices ( Lancaster and Knoblich, 2014 ; Camp et al, 2015 ; Blokzijl et al, 2016 ; Choi et al, 2016 ; Qian et al, 2016 ; Hu et al, 2018 ; Cho et al, 2021 ; Giandomenico et al, 2021 ; Holloway et al, 2021 ; Luo and Li, 2021 ). Each method offers its own advantages: spheroid can partially recreate the 3D structure of physiological brain tissue but presents challenges in controlling the size and composition in the culture.…”

Section: Things To Keep In Consideration Neuronal Aging With Induced ...mentioning

confidence: 99%

Accelerated neuronal aging in vitro ∼melting watch ∼

Inagaki

Yoshimatsu²,

Okano³

2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

In developed countries, the aging of the population and the associated increase in age-related diseases are causing major unresolved medical, social, and environmental matters. Therefore, research on aging has become one of the most important and urgent issues in life sciences. If the molecular mechanisms of the onset and progression of neurodegenerative diseases are elucidated, we can expect to develop disease-modifying methods to prevent neurodegeneration itself. Since the discovery of induced pluripotent stem cells (iPSCs), there has been an explosion of disease models using disease-specific iPSCs derived from patient-derived somatic cells. By inducing the differentiation of iPSCs into neurons, disease models that reflect the patient-derived pathology can be reproduced in culture dishes, and are playing an active role in elucidating new pathological mechanisms and as a platform for new drug discovery. At the same time, however, we are faced with a new problem: how to recapitulate aging in culture dishes. It has been pointed out that cells differentiated from pluripotent stem cells are juvenile, retain embryonic traits, and may not be fully mature. Therefore, attempts are being made to induce cell maturation, senescence, and stress signals through culture conditions. It has also been reported that direct conversion of fibroblasts into neurons can reproduce human neurons with an aged phenotype. Here, we outline some state-of-the-art insights into models of neuronal aging in vitro. New frontiers in which stem cells and methods for inducing differentiation of tissue regeneration can be applied to aging research are just now approaching, and we need to keep a close eye on them. These models are forefront and intended to advance our knowledge of the molecular mechanisms of aging and contribute to the development of novel therapies for human neurodegenerative diseases associated with aging.

show abstract

Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

Cited by 13 publications

References 155 publications

Brain and Retinal Organoids for Disease Modeling: The Importance of In Vitro Blood–Brain and Retinal Barriers Studies

Brain and Retinal Organoids for Disease Modeling: The Importance of In Vitro Blood–Brain and Retinal Barriers Studies

Human mini brains and spinal cords in a dish: Modeling strategies, current challenges, and prospective advances

Accelerated neuronal aging in vitro ∼melting watch ∼

Contact Info

Product

Resources

About