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Cells
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Stem Cells, Metabolism and Neurodegenerative Diseases
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Stem Cells, Metabolism and Neurodegenerative Diseases

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 16156

Special Issue Editors

Dr. Fábio G. Teixeira

E-Mail Website1 Website2
Guest Editor
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal
Interests: regenerative medicine; mesenchymal stem cells; stem cells secretome; bioreactor cell culture; exosomes; astrocyte reactivity; neuron-glia communication; 3D culture systems; focused ultrasound; Parkinson's disease
Dr. Pilar Baylina

E-Mail Website
Guest Editor
1. School of Health, Polytechnic Institute of Porto, 4200-072 Porto, Portugal
2. Laboratory of Medical and Industrial Biotechnology, 4200-374 Porto, Portugal
Interests: risk management; public health policies; infection management; drug resistance; phage therapy; biotechnology
Dr. Ruben Fernandes

E-Mail Website
Guest Editor
Laboratory of Medical and Industrial Biotechnology (LABMI), School of Health, Porto Polytechnic Institute, Porto, Portugal
Interests: medical biotechnology; metabolic disorders; diabetes; obesity; infection; bacteria drug resistance; cancer; radiation biology; omics; microbiome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Recent advances in stem cell technology have introduced enabling tools in pre-and clinical translation, presenting promising therapeutic outcomes to the conventional pharmacological/surgical treatments for CNS modeling and repair. Nevertheless, neurodegenerative diseases share a range of molecular and cellular alterations, namely protein accumulation, mitochondrial dysfunction, glutamate excitotoxicity, calcium load, proteolytic stress, oxidative stress, neuroinflammation, and aging, contributing to neuronal damage.

However, although we know that all these alterations are linked to the initiation and progression of neurodegenerative diseases, a lack of clarity regarding the possible cause underlying all the above molecular and cellular pathologies poses a significant challenge. Therefore, during the last years, it has been hypothesized that metabolic deficiency in certain vulnerable neuronal clusters, as well as metabolic shuttles, metabolic shifts and transporters disorders, could be a common underlying thread linking many dimensions of the disease. As such, in this issue a special focus will be given to stem cell therapeutics and how metabolic alterations or dysfunction could impact not only its therapeutical effect, but also the molecular, cellular, and system-level of neurodegenerative diseases.

Thus, the current Special Issue will accept original studies, reviews, and technical reports focusing on stem cell therapeutics, precision medicine, -omics, animal disease models, pre-and clinical studies, and cellular/molecular diagnostics.

Dr. Fábio G. Teixeira
Dr. Pilar Baylina
Dr. Ruben Fernandes
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stem cells
  • neurodegenerative diseases
  • metabolism dysfunction
  • disease modeling
  • precision medicine
  • (neuro)inflammation

Published Papers (5 papers)

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Research

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26 pages, 5303 KiB  
Article
The Metabolic Changes between Monolayer (2D) and Three-Dimensional (3D) Culture Conditions in Human Mesenchymal Stem/Stromal Cells Derived from Adipose Tissue
by Paulina Rybkowska, Klaudia Radoszkiewicz, Maria Kawalec, Dorota Dymkowska, Barbara Zabłocka, Krzysztof Zabłocki and Anna Sarnowska
Cells 2023, 12(1), 178; https://doi.org/10.3390/cells12010178 - 01 Jan 2023
Cited by 10 | Viewed by 3048
Abstract
Introduction: One of the key factors that may influence the therapeutic potential of mesenchymal stem/stromal cells (MSCs) is their metabolism. The switch between mitochondrial respiration and glycolysis can be affected by many factors, including the oxygen concentration and the spatial form of culture. [...] Read more.
Introduction: One of the key factors that may influence the therapeutic potential of mesenchymal stem/stromal cells (MSCs) is their metabolism. The switch between mitochondrial respiration and glycolysis can be affected by many factors, including the oxygen concentration and the spatial form of culture. This study compared the metabolic features of adipose-derived mesenchymal stem/stromal cells (ASCs) and dedifferentiated fat cells (DFATs) cultivated as monolayer or spheroid culture under 5% O2 concentration (physiological normoxia) and their impact on MSCs therapeutic abilities. Results: We observed that the cells cultured as spheroids had a slightly lower viability and a reduced proliferation rate but a higher expression of the stemness-related transcriptional factors compared to the cells cultured in monolayer. The three-dimensional culture form increased mtDNA content, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), especially in DFATs-3D population. The DFATs spheroids also demonstrated increased levels of Complex V proteins and higher rates of ATP production. Moreover, increased reactive oxygen species and lower intracellular lactic acid levels were also found in 3D culture. Conclusion: Our results may suggest that metabolic reconfiguration accompanies the transition from 2D to 3D culture and the processes of both mitochondrial respiration and glycolysis become more active. Intensified metabolism might be associated with the increased demand for energy, which is needed to maintain the expression of pluripotency genes and stemness state. Full article
(This article belongs to the Special Issue Stem Cells, Metabolism and Neurodegenerative Diseases)
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23 pages, 3918 KiB  
Article
Integrated Excitatory/Inhibitory Imbalance and Transcriptomic Analysis Reveals the Association between Dysregulated Synaptic Genes and Anesthetic-Induced Cognitive Dysfunction
by Yasheng Yan, Sarah Logan, Xiaojie Liu, Bixuan Chen, Congshan Jiang, Thiago Arzua, Ramani Ramchandran, Qing-song Liu and Xiaowen Bai
Cells 2022, 11(16), 2497; https://doi.org/10.3390/cells11162497 - 11 Aug 2022
Cited by 3 | Viewed by 1728
Abstract
Emerging evidence from human epidemiologic and animal studies has demonstrated that developmental anesthesia neurotoxicity could cause long-term cognitive deficits and behavioral problems. However, the underlying mechanisms remain largely unknown. We conducted an electrophysiological analysis of synapse activity and a transcriptomic assay of 24,881 [...] Read more.
Emerging evidence from human epidemiologic and animal studies has demonstrated that developmental anesthesia neurotoxicity could cause long-term cognitive deficits and behavioral problems. However, the underlying mechanisms remain largely unknown. We conducted an electrophysiological analysis of synapse activity and a transcriptomic assay of 24,881 mRNA expression on hippocampal tissues from postnatal day 60 (P60) mice receiving propofol exposure at postnatal day 7 (P7). We found that developmentally propofol-exposed P60 mouse hippocampal neurons displayed an E/I imbalance, compared with control mice as evidenced by the decreased excitation and increased inhibition. We found that propofol exposure at P7 led to the abnormal expression of 317 mRNAs in the hippocampus of P60 mice, including 23 synapse-related genes. Various bioinformatic analyses revealed that these abnormally expressed synaptic genes were associated with the function and development of synapse activity and plasticity, E/I balance, behavior, and cognitive impairment. Our findings suggest that the altered E/I balance may constitute a mechanism for propofol-induced long-term impaired learning and memory in mice. The transcriptomic and bioinformatic analysis of these dysregulated genes related to synaptic function paves the way for development of therapeutic strategies against anesthetic neurodegeneration through the restoration of E/I balance and the modification of synaptic gene expression. Full article
(This article belongs to the Special Issue Stem Cells, Metabolism and Neurodegenerative Diseases)
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16 pages, 5767 KiB  
Article
Restoration of BDNF, DARPP32, and D2R Expression Following Intravenous Infusion of Human Immature Dental Pulp Stem Cells in Huntington’s Disease 3-NP Rat Model
by Cristiane Valverde Wenceslau, Dener Madeiro de Souza, Nicole Caroline Mambelli-Lisboa, Leandro Hideki Ynoue, Rodrigo Pinheiro Araldi, Joyce Macedo da Silva, Eduardo Pagani, Monica Santoro Haddad and Irina Kerkis
Cells 2022, 11(10), 1664; https://doi.org/10.3390/cells11101664 - 17 May 2022
Cited by 11 | Viewed by 2366
Abstract
Huntington’s disease (HD) is a neurodegenerative inherited genetic disorder, which leads to the onset of motor, neuropsychiatric and cognitive disturbances. HD is characterized by the loss of gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). To date, there is no treatment for HD. Mesenchymal [...] Read more.
Huntington’s disease (HD) is a neurodegenerative inherited genetic disorder, which leads to the onset of motor, neuropsychiatric and cognitive disturbances. HD is characterized by the loss of gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). To date, there is no treatment for HD. Mesenchymal stem cells (MSCs) provide a substantial therapeutic opportunity for the HD treatment. Herein, we investigated the therapeutic potential of human immature dental pulp stem cells (hIDPSC), a special type of MSC originated from the neural crest, for HD treatment. Two different doses of hIDPSC were intravenously administrated in a subacute 3-nitropropionic acid (3NP)-induced rat model. We demonstrated hIDPSC homing in the striatum, cortex and subventricular zone using specific markers for human cells. Thirty days after hIDPSC administration, the cells found in the brain are still express hallmarks of undifferentiated MSC. Immunohistochemistry quantities analysis revealed a significant increase in the number of BDNF, DARPP32 and D2R positive stained cells in the striatum and cortex in the groups that received hIDPSC. The differences were more expressive in animals that received only one administration of hIDPSC. Altogether, these data suggest that the intravenous administration of hIDPSCs can restore the BDNF, DARPP32 and D2R expression, promoting neuroprotection and neurogenesis. Full article
(This article belongs to the Special Issue Stem Cells, Metabolism and Neurodegenerative Diseases)
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Review

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60 pages, 2382 KiB  
Review
Neural Progenitor Cells and the Hypothalamus
by Evanthia A. Makrygianni and George P. Chrousos
Cells 2023, 12(14), 1822; https://doi.org/10.3390/cells12141822 - 11 Jul 2023
Cited by 2 | Viewed by 3649
Abstract
Neural progenitor cells (NPCs) are multipotent neural stem cells (NSCs) capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. In the postnatal/adult brain, NPCs are primarily located in the subventricular zone (SVZ) of the lateral ventricles (LVs) and subgranular zone (SGZ) of [...] Read more.
Neural progenitor cells (NPCs) are multipotent neural stem cells (NSCs) capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. In the postnatal/adult brain, NPCs are primarily located in the subventricular zone (SVZ) of the lateral ventricles (LVs) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). There is evidence that NPCs are also present in the postnatal/adult hypothalamus, a highly conserved brain region involved in the regulation of core homeostatic processes, such as feeding, metabolism, reproduction, neuroendocrine integration and autonomic output. In the rodent postnatal/adult hypothalamus, NPCs mainly comprise different subtypes of tanycytes lining the wall of the 3rd ventricle. In the postnatal/adult human hypothalamus, the neurogenic niche is constituted by tanycytes at the floor of the 3rd ventricle, ependymal cells and ribbon cells (showing a gap-and-ribbon organization similar to that in the SVZ), as well as suprachiasmatic cells. We speculate that in the postnatal/adult human hypothalamus, neurogenesis occurs in a highly complex, exquisitely sophisticated neurogenic niche consisting of at least four subniches; this structure has a key role in the regulation of extrahypothalamic neurogenesis, and hypothalamic and extrahypothalamic neural circuits, partly through the release of neurotransmitters, neuropeptides, extracellular vesicles (EVs) and non-coding RNAs (ncRNAs). Full article
(This article belongs to the Special Issue Stem Cells, Metabolism and Neurodegenerative Diseases)
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40 pages, 1282 KiB  
Review
Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities
by Bruna Araújo, Rita Caridade-Silva, Carla Soares-Guedes, Joana Martins-Macedo, Eduardo D. Gomes, Susana Monteiro and Fábio G. Teixeira
Cells 2022, 11(18), 2908; https://doi.org/10.3390/cells11182908 - 17 Sep 2022
Cited by 26 | Viewed by 4572
Abstract
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Clinically, it is characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroinflammation can play a role in PD pathophysiology, [...] Read more.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Clinically, it is characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroinflammation can play a role in PD pathophysiology, being associated with its onset and progression. Nevertheless, several key points concerning the neuroinflammatory process in PD remain to be answered. Bearing this in mind, in the present review, we cover the impact of neuroinflammation on PD by exploring the role of inflammatory cells (i.e., microglia and astrocytes) and the interconnections between the brain and the peripheral system. Furthermore, we discuss both the innate and adaptive immune responses regarding PD pathology and explore the gut–brain axis communication and its influence on the progression of the disease. Full article
(This article belongs to the Special Issue Stem Cells, Metabolism and Neurodegenerative Diseases)
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