A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Park, Jong Chan; Jang, Soyeong; Lee, Dongjoon; Lee, Jeongha; Kang, Uiryong; Chang, Hyeyeon; Kim, Haeng Jun; Han, Sun Ho; Seo, Jinsoo; Choi, Murim; Lee, Dong Hoon; Byun, Min Soo; Yi, Dahyun; Cho, Kwang Hyun; Mook‐Jung, Inhee

doi:10.1038/s41467-020-20440-5

Cited by 126 publications

(124 citation statements)

References 80 publications

(49 reference statements)

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“…Most recently, Park et al have developed a network-based drug-screening platform by integrating mathematical modeling and hPDBOs with the AD pathological features. Using this platform, they have identified several FDA-approved drugs as candidates for curing AD [ 103 ]. Taken together, these studies have demonstrated that hPDBOs indeed represent a more ideal and efficient model for AD modeling and drug screening.…”

Section: Bos For Modeling Neurodegenerative Disordersmentioning

confidence: 99%

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

Luo

2021

Cell Biosci

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The sheer complexities of brain and resource limitation of human brain tissue greatly hamper our understanding of the brain disorders and cancers. Recently developed three-dimensional (3D) brain organoids (BOs) are self-organized and spontaneously differentiated from human pluripotent stem cells (hPSCs) in vitro, which exhibit similar features with cell type diversity, structural organization, and functional connectivity as the developing human brain. Based on these characteristics, hPSC-derived BOs (hPDBOs) provide new opportunities to recapitulate the complicated processes during brain development, neurodegenerative disorders, and brain cancers in vitro. In this review, we will provide an overview of existing BO models and summarize the applications of this technology in modeling the neural disorders and cancers. Furthermore, we will discuss the challenges associated with their use as in vitro models for disease modeling and the potential future direction.

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Section: Bos For Modeling Neurodegenerative Disordersmentioning

confidence: 99%

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

Luo

2021

Cell Biosci

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“…In addition to studying toxic Aβ species, 3D culture models such as 3D cerebral organoids have been used to test if specific antibodies can block tau pathology [ 50 , 95 , 110 , 111 , 112 ]. Determination of the efficacy and optimal dosage of small molecule drug candidates can also be performed using hiPSC-based AD models.…”

Section: Disease Modeling Using Hipscsmentioning

confidence: 99%

Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

Trudler

Ghatak

Lipton

2021

IJMS

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Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

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“…Lancaster et al generated cerebral organoids from iPSCs derived from a patient with microcephaly and demonstrated premature neuronal differentiation, which resembled the disease phenotypes [ 15 ]. Moreover, cerebral organoids have been applied for the disease modeling of many central nervous disorders, including Alzheimer’s disease [ 55 , 56 , 57 , 58 , 59 ], frontotemporal dementia [ 60 ], Huntington’s disease [ 61 ], and Parkinson’s disease [ 62 , 63 ]. We previously established a disease model of congenital hypopituitarism with OTX2 mutation using patient-derived iPSCs.…”

Section: Hpsc-derived Organoidsmentioning

confidence: 99%

Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques

Matsumoto

Yamamoto

Takahashi

2021

IJMS

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Human pluripotent stem cells (hPSCs) are grouped into two cell types; embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). hESCs have provided multiple powerful platforms to study human biology, including human development and diseases; however, there were difficulties in the establishment of hESCs from human embryo and concerns over its ethical issues. The discovery of hiPSCs has expanded to various applications in no time because hiPSCs had already overcome these problems. Many hPSC-based studies have been performed using two-dimensional monocellular culture methods at the cellular level. However, in many physiological and pathophysiological conditions, intra- and inter-organ interactions play an essential role, which has hampered the establishment of an appropriate study model. Therefore, the application of recently developed technologies, such as three-dimensional organoids, bioengineering, and organ-on-a-chip technology, has great potential for constructing multicellular tissues, generating the functional organs from hPSCs, and recapitulating complex tissue functions for better biological research and disease modeling. Moreover, emerging techniques, such as single-cell transcriptomics, spatial transcriptomics, and artificial intelligence (AI) allowed for a denser and more precise analysis of such heterogeneous and complex tissues. Here, we review the applications of hPSCs to construct complex organs and discuss further prospects of disease modeling and drug discovery based on these PSC-derived organs.

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A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Cited by 126 publications

References 80 publications

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

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

Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

Complex Organ Construction from Human Pluripotent Stem Cells for Biological Research and Disease Modeling with New Emerging Techniques

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