Induced Pluripotent Stem Cells in Basic and Translational Research

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 9282

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Guest Editor
1. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78245-0549, USA
2. Department of Radiology, Long School of Medicine, University of Texas Health San Antonio, San Antonio, TX 78229-3900, USA
Interests: Parkinson’s disease; stroke; traumatic brain injury (TBI); multiple sclerosis (MS); human neural stem cells (NSCs); non human primate studies
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Special Issue Information

Dear Colleagues,

The ability to turn adult skin, blood, or other types of somatic cells into a pluripotent stem cell has opened new frontiers in basic biology and medical research. An induced pluripotent stem cell (iPSC) is created by reprogramming any cell of the human body into the pluripotent developmental stage. The reprogrammed cells are then able to generate a virtually unlimited number of progeny capable of differentiating into organ-specific specialized functional cells. IPSCs offer a unique research platform for modeling gene variants and monogenic causal genes to characterize gene-associated function and dysfunction, for drug screening, for cell therapy, and for personalized medicine. This Special Issue focuses on recent advances in iPSC basic and translational research, specifically cellular differentiation, the generation of specific lineages, tissue morphogenesis and 3D culture systems, the pathogenesis of diseases, in vitro systems for drug discovery, and the development of innovative therapeutic interventions.

Dr. Marcel M. Daadi
Guest Editor

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Published Papers (3 papers)

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20 pages, 3977 KiB  
Article
LRRK2 Attenuates Antioxidant Response in Familial Parkinson’s Disease Derived Neural Stem Cells
by Jeffrey Kim, Etienne W. Daadi, Elyas Sebastien Daadi, Thomas Oh, Michela Deleidi and Marcel M. Daadi
Cells 2023, 12(21), 2550; https://doi.org/10.3390/cells12212550 - 31 Oct 2023
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Abstract
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons which leads to impaired motor and cognitive functions. PD is predominantly an idiopathic disease; however, about 5% of cases are linked to hereditary mutations. The [...] Read more.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons which leads to impaired motor and cognitive functions. PD is predominantly an idiopathic disease; however, about 5% of cases are linked to hereditary mutations. The most common mutation in both familial and sporadic PD is the G2019S mutation of leucine-rich repeat kinase 2 (LRRK2). Currently, it is not fully understood how this mutation leads to PD pathology. In this study, we isolated self-renewable, multipotent neural stem cells (NSCs) from induced pluripotent stem cells (iPSCs) harboring the G2019S LRRK2 mutation and compared them with their isogenic gene corrected counterparts using single-cell RNA-sequencing. Unbiased single-cell transcriptomic analysis revealed perturbations in many canonical pathways, specifically NRF2-mediated oxidative stress response, and glutathione redox reactions. Through various functional assays, we observed that G2019S iPSCs and NSCs exhibit increased basal levels of reactive oxygen species (ROS). We demonstrated that mutant cells show significant increase in the expression for KEAP1 and decrease in NRF2 associated with a reduced antioxidant response. The decreased viability of mutant NSCs in the H2O2-induced oxidative stress assay was rescued by two potent antioxidant drugs, PrC-210 at concentrations of 500 µM and 1 mM and Edaravone at concentrations 50 µM and 100 µM. Our data suggest that the hyperactive LRRK2 G2019S kinase activity leads to increase in KEAP1, which binds NRF2 and leads to its degradation, reduction in the antioxidant response, increased ROS, mitochondria dysfunction and cell death observed in the PD phenotype. Full article
(This article belongs to the Special Issue Induced Pluripotent Stem Cells in Basic and Translational Research)
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15 pages, 4101 KiB  
Article
Lewy Body-like Pathology and Loss of Dopaminergic Neurons in Midbrain Organoids Derived from Familial Parkinson’s Disease Patient
by Andrea Becerra-Calixto, Abhisek Mukherjee, Santiago Ramirez, Sofia Sepulveda, Tirthankar Sinha, Rabab Al-Lahham, Nicole De Gregorio, Camila Gherardelli and Claudio Soto
Cells 2023, 12(4), 625; https://doi.org/10.3390/cells12040625 - 15 Feb 2023
Cited by 6 | Viewed by 3133
Abstract
Progressive accumulation of α-Synuclein (αSyn) in Lewy bodies (LBs) and loss of dopaminergic (DA) neurons are the hallmark pathological features of Parkinson’s disease (PD). Although currently available in vitro and in vivo models have provided crucial information about PD pathogenesis, the mechanistic link [...] Read more.
Progressive accumulation of α-Synuclein (αSyn) in Lewy bodies (LBs) and loss of dopaminergic (DA) neurons are the hallmark pathological features of Parkinson’s disease (PD). Although currently available in vitro and in vivo models have provided crucial information about PD pathogenesis, the mechanistic link between the progressive accumulation of αSyn into LBs and the loss of DA neurons is still unclear. To address this, it is critical to model LB formation and DA neuron loss, the two key neuropathological aspects of PD, in a relevant in vitro system. In this study, we developed a human midbrain-like organoid (hMBO) model of PD. We demonstrated that hMBOs generated from induced pluripotent stem cells (hiPSCs), derived from a familial PD (fPD) patient carrying αSyn gene (SNCA) triplication accumulate pathological αSyn over time. These cytoplasmic inclusions spatially and morphologically resembled diverse stages of LB formation and were composed of key markers of LBs. Importantly, the progressive accumulation of pathological αSyn was paralleled by the loss of DA neurons and elevated apoptosis. The model developed in this study will complement the existing in vitro models of PD and will provide a unique platform to study the spatiotemporal events governing LB formation and their relation with neurodegeneration. Furthermore, this model will also be beneficial for in vitro screening and the development of therapeutic compounds. Full article
(This article belongs to the Special Issue Induced Pluripotent Stem Cells in Basic and Translational Research)
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43 pages, 5065 KiB  
Review
Development and In Vitro Differentiation of Schwann Cells
by Sarah Janice Hörner, Nathalie Couturier, Daniele Caroline Gueiber, Mathias Hafner and Rüdiger Rudolf
Cells 2022, 11(23), 3753; https://doi.org/10.3390/cells11233753 - 24 Nov 2022
Cited by 6 | Viewed by 4287
Abstract
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human [...] Read more.
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human Schwann cells are challenging to obtain in large quantities, in vitro differentiation from other cell types presents an alternative. Here, we first review the current knowledge on the developmental signaling mechanisms that determine neural crest and Schwann cell differentiation in vivo. Next, an overview of studies on the in vitro differentiation of Schwann cells from multipotent stem cell sources is provided. The molecules frequently used in those protocols and their involvement in the relevant signaling pathways are put into context and discussed. Focusing on hiPSC- and hESC-based studies, different protocols are described and compared, regarding cell sources, differentiation methods, characterization of cells, and protocol efficiency. A brief insight into developments regarding the culture and differentiation of Schwann cells in 3D is given. In summary, this contribution provides an overview of the current resources and methods for the differentiation of Schwann cells, it supports the comparison and refinement of protocols and aids the choice of suitable methods for specific applications. Full article
(This article belongs to the Special Issue Induced Pluripotent Stem Cells in Basic and Translational Research)
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