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The Link between Stem Cells and Nervous System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 8142

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Guest Editor
Experimental Neurology Unit and Milan Center for Neuroscience, School of Medicine and Surgery, Milano-Bicocca University, 20900 Monza, Italy
Interests: mesenchymal stem cell neuroprotection; neurotoxicity; neuroprotective molecular mechanisms; peripheral neuropathies; pancreatic islet transplantation for diabetes treatment
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Special Issue Information

Dear Colleagues, 

Stem cells are defined as a class of cells capable of self-renewal and differentiation into a variety of cells. When considering neurological diseases, there are important problems related to treatment, such as poor prognosis and serious impacts on patient’s quality of life. People are exploring the use of stem cells to treat neurological diseases in humans.

Previous studies have confirmed that neurons or glial cells derived from embryonic stem cells or neural stem cells have the ability to self-renew and can be used to treat various neurological diseases. However, there are still many limitations, including how to get cells to migrate to the right site and differentiate correctly into the specific, desired type of nerve cells. Furthermore, if not well controlled, neural stem cells can form tumor cells, which will have a serious impact on the patient.

This Special Issue will discuss the regeneration mechanism of stem cells in physiological and pathological conditions and collect the research progress of stem cells for the treatment of neurological diseases. This Special Issue also aims to provide new treatment ideas for some currently incurable neurological diseases.

Dr. Arianna Scuteri
Guest Editor

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Keywords

  • stem cells
  • embryonic stem cells
  • induced pluripotent
  • stem cell-derived extracellular vesicles
  • nervous system disease
  • neural regeneration

Published Papers (4 papers)

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Research

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17 pages, 4233 KiB  
Article
Deciphering the Molecular Mechanisms of Autonomic Nervous System Neuron Induction through Integrative Bioinformatics Analysis
by Yuzo Takayama, Yuka Akagi and Yasuyuki S. Kida
Int. J. Mol. Sci. 2023, 24(10), 9053; https://doi.org/10.3390/ijms24109053 - 21 May 2023
Cited by 2 | Viewed by 2028
Abstract
In vitro derivation of human neurons in the autonomic nervous system (ANS) is an important technology, given its regulatory roles in maintaining homeostasis in the human body. Although several induction protocols for autonomic lineages have been reported, the regulatory machinery remains largely undefined, [...] Read more.
In vitro derivation of human neurons in the autonomic nervous system (ANS) is an important technology, given its regulatory roles in maintaining homeostasis in the human body. Although several induction protocols for autonomic lineages have been reported, the regulatory machinery remains largely undefined, primarily due to the absence of a comprehensive understanding of the molecular mechanism regulating human autonomic induction in vitro. In this study, our objective was to pinpoint key regulatory components using integrated bioinformatics analysis. A protein–protein interaction network construction for the proteins encoded by the differentially expressed genes from our RNA sequencing data, and conducting subsequent module analysis, we identified distinct gene clusters and hub genes involved in the induction of autonomic lineages. Moreover, we analyzed the impact of transcription factor (TF) activity on target gene expression, revealing enhanced autonomic TF activity that could lead to the induction of autonomic lineages. The accuracy of this bioinformatics analysis was corroborated by employing calcium imaging to observe specific responses to certain ANS agonists. This investigation offers novel insights into the regulatory machinery in the generation of neurons in the ANS, which would be valuable for further understanding and precise regulation of autonomic induction and differentiation. Full article
(This article belongs to the Special Issue The Link between Stem Cells and Nervous System)
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15 pages, 2999 KiB  
Article
Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells
by Laureana Muok, Chang Liu, Xingchi Chen, Colin Esmonde, Peggy Arthur, Xueju Wang, Mandip Singh, Tristan Driscoll and Yan Li
Int. J. Mol. Sci. 2023, 24(8), 7660; https://doi.org/10.3390/ijms24087660 - 21 Apr 2023
Cited by 1 | Viewed by 2682
Abstract
The choroid plexus (ChP) is a complex structure in the human brain that is responsible for the secretion of cerebrospinal fluid (CSF) and forming the blood–CSF barrier (B-CSF-B). Human-induced pluripotent stem cells (hiPSCs) have shown promising results in the formation of brain organoids [...] Read more.
The choroid plexus (ChP) is a complex structure in the human brain that is responsible for the secretion of cerebrospinal fluid (CSF) and forming the blood–CSF barrier (B-CSF-B). Human-induced pluripotent stem cells (hiPSCs) have shown promising results in the formation of brain organoids in vitro; however, very few studies to date have generated ChP organoids. In particular, no study has assessed the inflammatory response and the extracellular vesicle (EV) biogenesis of hiPSC-derived ChP organoids. In this study, the impacts of Wnt signaling on the inflammatory response and EV biogenesis of ChP organoids derived from hiPSCs was investigated. During days 10–15, bone morphogenetic protein 4 was added along with (+/−) CHIR99021 (CHIR, a small molecule GSK-3β inhibitor that acts as a Wnt agonist). At day 30, the ChP organoids were characterized by immunocytochemistry and flow cytometry for TTR (~72%) and CLIC6 (~20%) expression. Compared to the −CHIR group, the +CHIR group showed an upregulation of 6 out of 10 tested ChP genes, including CLIC6 (2-fold), PLEC (4-fold), PLTP (2–4-fold), DCN (~7-fold), DLK1 (2–4-fold), and AQP1 (1.4-fold), and a downregulation of TTR (0.1-fold), IGFBP7 (0.8-fold), MSX1 (0.4-fold), and LUM (0.2–0.4-fold). When exposed to amyloid beta 42 oligomers, the +CHIR group had a more sensitive response as evidenced by the upregulation of inflammation-related genes such as TNFα, IL-6, and MMP2/9 when compared to the −CHIR group. Developmentally, the EV biogenesis markers of ChP organoids showed an increase over time from day 19 to day 38. This study is significant in that it provides a model of the human B-CSF-B and ChP tissue for the purpose of drug screening and designing drug delivery systems to treat neurological disorders such as Alzheimer’s disease and ischemic stroke. Full article
(This article belongs to the Special Issue The Link between Stem Cells and Nervous System)
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Review

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16 pages, 719 KiB  
Review
Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases
by Haneul Kim, Gon Sup Kim, Sang-Hwan Hyun and Eunhye Kim
Int. J. Mol. Sci. 2023, 24(23), 17006; https://doi.org/10.3390/ijms242317006 - 30 Nov 2023
Viewed by 1099
Abstract
Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in [...] Read more.
Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in generating in vitro neuromuscular models using engineering approaches to recapitulate the complex physical and biochemical microenvironments of 3D human neuromuscular tissues. In this review, we discuss recent studies focusing on the development of in vitro co-culture models of human motor neurons and skeletal muscles, with the pros and cons of each approach. Furthermore, we explain how neuromuscular in vitro models recapitulate certain aspects of specific NMDs, including amyotrophic lateral sclerosis and muscular dystrophy. Research on neuromuscular organoids (NMO) will continue to co-develop to better mimic tissues in vivo and will provide a better understanding of the development of the neuromuscular tissue, mechanisms of NMD action, and tools applicable to preclinical studies, including drug screening and toxicity tests. Full article
(This article belongs to the Special Issue The Link between Stem Cells and Nervous System)
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12 pages, 1097 KiB  
Review
Role of Tunneling Nanotubes in the Nervous System
by Olga Tarasiuk and Arianna Scuteri
Int. J. Mol. Sci. 2022, 23(20), 12545; https://doi.org/10.3390/ijms232012545 - 19 Oct 2022
Cited by 3 | Viewed by 1706
Abstract
Cellular communication and the transfer of information from one cell to another is crucial for cell viability and homeostasis. During the last decade, tunneling nanotubes (TNTs) have attracted scientific attention, not only as a means of direct intercellular communication, but also as a [...] Read more.
Cellular communication and the transfer of information from one cell to another is crucial for cell viability and homeostasis. During the last decade, tunneling nanotubes (TNTs) have attracted scientific attention, not only as a means of direct intercellular communication, but also as a possible system to transport biological cargo between distant cells. Peculiar TNT characteristics make them both able to increase cellular survival capacities, as well as a potential target of neurodegenerative disease progression. Despite TNT formation having been documented in a number of cell types, the exact mechanisms triggering their formation are still not completely known. In this review, we will summarize and highlight those studies focusing on TNT formation in the nervous system, as well as their role in neurodegenerative diseases. Moreover, we aim to stress some possible mechanisms and important proteins probably involved in TNT formation in the nervous system. Full article
(This article belongs to the Special Issue The Link between Stem Cells and Nervous System)
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