Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease

Pasteuning-Vuhman, Svetlana; Jongh, Rianne de; Timmers, Annabel; Pasterkamp, R. Jeroen

doi:10.1016/j.molmed.2020.09.013

Cited by 51 publications

(37 citation statements)

References 107 publications

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“…Methods for differentiating other key brain types including astrocytes (Lundin et al., 2018), microglia (Hasselmann & Blurton‐Jones, 2020), and pericytes (Faal et al., 2019) have also been developed and many of these protocols have already been integrated into MPS (Appelt‐Menzel et al., 2017; Prots et al., 2018; Usenovic et al., 2015). While integration of iPSC technologies may have the potential to greatly improve translational relevance for these models, as outlined in reviews by A. Sharma et al (2020) and Pasteuning‐Vuhman et al (2020), to be widely adopted, they need to be carefully characterized both phenotypically and functionally. Without careful phenotypic characterization, cell identity of differentiated cells can be mistaken.…”

Section: Future Development and Challengesmentioning

confidence: 99%

Advances in microfluidic in vitro systems for neurological disease modeling

Holloway

Willaime‐Morawek

Siow

et al. 2021

J of Neuroscience Research

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Section: Future Development and Challengesmentioning

confidence: 99%

Advances in microfluidic in vitro systems for neurological disease modeling

Holloway

Willaime‐Morawek

Siow

et al. 2021

J of Neuroscience Research

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“…While most of these studies have focused on neuronal pathology, other brain cell types have gained interest, and publications in this area are expected to increase in the following years. iPSC-derived models have a great potential in drug screening applications and could potentially bridge the gap between preclinical and clinical studies in NDDs [ 190 ]. However, this field is still in the early days, and only a few studies have reported drug screening applications.…”

Section: Human-induced Pluripotent Stem Cells In Blood–brain Barrier Modelingmentioning

confidence: 99%

Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells

Sonninen

Peltonen

et al. 2021

IJMS

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The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.

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“…High-throughput screening paradigms are another advance in organoid-based drug screening, which was recently demonstrated in the kidney (Czerniecki et al, 2018). The generation of organoids based on specific diseases or even specific individuals is expected to become a powerful tool for precision therapy (Eglen and Randle, 2015;Walsh et al, 2016;Pasteuning-Vuhman et al, 2020).…”

Section: Drug Screening and Precision Therapymentioning

confidence: 99%

To Better Generate Organoids, What Can We Learn From Teratomas?

Gao

et al. 2021

Front. Cell Dev. Biol.

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The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

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Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease

Cited by 51 publications

References 107 publications

Advances in microfluidic in vitro systems for neurological disease modeling

Advances in microfluidic in vitro systems for neurological disease modeling

Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells

To Better Generate Organoids, What Can We Learn From Teratomas?

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