10th Anniversary of Cells—Advances in Cell Microenvironment

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

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 44195

Special Issue Editors


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Guest Editor
Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases (DZNE), Leipziger Str. 44/64, 39120 Magdeburg, Germany
Interests: extracellular matrix; cell adhesion; synaptogenesis; synaptic plasticity; intrinsic plasticity; dementia; schizophrenia; mental retardation; epilepsy
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Guest Editor
Illawarra Health and Medical Research Institute, and Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia
Interests: extracellular proteostasis; chaperones; protein folding; cytotoxicity; flow cytometry; optical microscopy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
UCL Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Interests: astrocytes; synaptic plasticity; mossy fibre circuitry of the hippocampus; neuroglia

Special Issue Information

Dear Colleagues,

The year 2021 marks the 10th anniversary of the publication of Cells. We are delighted and proud to celebrate this momentous event with a series of Special Issues and events. To date, the journal has published more than 7000 papers, and the journal website attracts more than 50,000 monthly page views. We would like to express our sincerest thanks to our readers, innumerable authors, anonymous peer reviewers, editors, and all the people working in some way for the journal who have made substantial contributions over the years. Without your support, we would never have made it this far.

To mark this important milestone, a Special Issue entitled “10th Anniversary of Cells—Advances in Cell Microenvironment” is being launched. This Special Issue will collect research articles and high-quality review papers in the research fields. We kindly encourage all research groups working in the Cell Microenvironment areas to make contributions to this Special Issue.

For details about the Cells 2021 Best Paper Awards for Anniversary Special Issues, please click here (https://www.mdpi.com/journal/cells/awards.pdf/0/pdf_32_2021_2_award.pdf).

Prof. Dr. Alexander Dityatev
Prof. Dr. Mark R. Wilson
Prof. Dr. Dmitri Rusakov
Guest Editors

Manuscript Submission Information

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Published Papers (14 papers)

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Research

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16 pages, 7746 KiB  
Article
Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses
by Giselle Cheung, Oana Chever, Astrid Rollenhagen, Nicole Quenech’du, Pascal Ezan, Joachim H. R. Lübke and Nathalie Rouach
Cells 2023, 12(8), 1133; https://doi.org/10.3390/cells12081133 - 11 Apr 2023
Cited by 2 | Viewed by 2122
Abstract
Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and [...] Read more.
Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43−/−), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43−/− mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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15 pages, 16259 KiB  
Article
Heparan Sulfates Regulate Axonal Excitability and Context Generalization through Ca2+/Calmodulin-Dependent Protein Kinase II
by Inseon Song, Tatiana Kuznetsova, David Baidoe-Ansah, Hadi Mirzapourdelavar, Oleg Senkov, Hussam Hayani, Andrey Mironov, Rahul Kaushik, Michael Druzin, Staffan Johansson and Alexander Dityatev
Cells 2023, 12(5), 744; https://doi.org/10.3390/cells12050744 - 25 Feb 2023
Viewed by 1677
Abstract
Our previous studies demonstrated that enzymatic removal of highly sulfated heparan sulfates with heparinase 1 impaired axonal excitability and reduced expression of ankyrin G at the axon initial segments in the CA1 region of the hippocampus ex vivo, impaired context discrimination in vivo, [...] Read more.
Our previous studies demonstrated that enzymatic removal of highly sulfated heparan sulfates with heparinase 1 impaired axonal excitability and reduced expression of ankyrin G at the axon initial segments in the CA1 region of the hippocampus ex vivo, impaired context discrimination in vivo, and increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity in vitro. Here, we show that in vivo delivery of heparinase 1 in the CA1 region of the hippocampus elevated autophosphorylation of CaMKII 24 h after injection in mice. Patch clamp recording in CA1 neurons revealed no significant heparinase effects on the amplitude or frequency of miniature excitatory and inhibitory postsynaptic currents, while the threshold for action potential generation was increased and fewer spikes were generated in response to current injection. Delivery of heparinase on the next day after contextual fear conditioning induced context overgeneralization 24 h after injection. Co-administration of heparinase with the CaMKII inhibitor (autocamtide-2-related inhibitory peptide) rescued neuronal excitability and expression of ankyrin G at the axon initial segment. It also restored context discrimination, suggesting the key role of CaMKII in neuronal signaling downstream of heparan sulfate proteoglycans and highlighting a link between impaired CA1 pyramidal cell excitability and context generalization during recall of contextual memories. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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18 pages, 4394 KiB  
Article
Cord Blood Plasma and Placental Mesenchymal Stem Cells-Derived Exosomes Increase Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells While Maintaining Their Stemness
by Rasha S. Teleb, Amal Abdul-Hafez, Amira Othman, Ahmed El-Abd Ahmed, Abdelrahman A. Elsaid, Hattan Arif, Ahmed A. Zarea, Mohammed Abdulmageed, Hend Mohamed, Sherif Abdelfattah Ibrahim, Ranga P. Thiruvenkataramani, Tarek Mohamed, Masamitsu Kanada, Burra V. Madhukar, Myrna Gonzalez Arellano, Mohammed M. Sayed, Heba M. Qubaisy and Said A. Omar
Cells 2023, 12(2), 250; https://doi.org/10.3390/cells12020250 - 7 Jan 2023
Cited by 3 | Viewed by 4086
Abstract
Background: Mesenchymal stem cells (MSCs) have been used for ex vivo expansion of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) to maintain their primitive characters and long-term reconstitution abilities during transplantation. Therapeutic effects of MSCs mainly rely on paracrine mechanisms, including secretion [...] Read more.
Background: Mesenchymal stem cells (MSCs) have been used for ex vivo expansion of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) to maintain their primitive characters and long-term reconstitution abilities during transplantation. Therapeutic effects of MSCs mainly rely on paracrine mechanisms, including secretion of exosomes (Exos). The objective of this study was to examine the effect of cord blood plasma (CBP)-derived Exos (CBP Exos) and Placental MSCs-derived Exos (MSCs Exos) on the expansion of UCB HSCs to increase their numbers and keep their primitive characteristics. Methods: CD34+ cells were isolated from UCB, cultured for 10 days, and the expanded HSCs were sub-cultured in semisolid methylcellulose media for primitive colony forming units (CFUs) assay. MSCs were cultured from placental chorionic plates. Results: CBP Exos and MSCs Exos compared with the control group significantly increased the number of total nucleated cells (TNCs), invitro expansion of CD34+ cells, primitive subpopulations of CD34+38+ and CD34+38Lin cells (p < 0.001). The expanded cells showed a significantly higher number of total CFUs in the Exos groups (p < 0.01). Conclusion: CBP- and placental-derived exosomes are associated with significant ex vivo expansion of UCB HSCs, while maintaining their primitive characters and may eliminate the need for transplantation of an additional unit of UCB. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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15 pages, 1461 KiB  
Article
Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome
by Ramtin Zargari Marandi, Mette Jørgensen, Emma Elizabeth Ilett, Jens Christian Nørgaard, Marc Noguera-Julian, Roger Paredes, Jens D. Lundgren, Henrik Sengeløv and Cameron Ross MacPherson
Cells 2022, 11(24), 4089; https://doi.org/10.3390/cells11244089 - 16 Dec 2022
Cited by 2 | Viewed by 2764
Abstract
Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) [...] Read more.
Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore. Microbial abundance profiles were estimated using ensembles of Kaiju, Kraken2, and DeepMicrobes calls followed by dimensionality reduction. The area under the curve (AUC) was used to evaluate classification of the samples (aGvHD vs. none) using an elastic net to test the relevance of metagenomic data. Clinical data included the underlying disease (leukemia vs. other hematological malignancies), recipient age, and sex. Among 172 aHSCT patients of whom 42 developed aGVHD post transplantation, a total of 181 pre-transplant tool samples were analyzed. The top performing model predicting risk of aGVHD included a reduced species profile (AUC = 0.672). Beta diversity (37% in Jaccard’s Nestedness by mean fold change, p < 0.05) was lower in those developing aGvHD. Ten bacterial species including Prevotella and Eggerthella genera were consistently found to associate with aGvHD in indicator species analysis, as well as relief and impurity-based algorithms. The findings support the hypothesis on potential associations between gut microbiota and aGvHD based on a data-driven approach to MWAS. This highlights the need and relevance of routine stool collection for the discovery of novel biomarkers. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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15 pages, 2253 KiB  
Article
Structural Heterogeneity of the GABAergic Tripartite Synapse
by Cindy Brunskine, Stefan Passlick and Christian Henneberger
Cells 2022, 11(19), 3150; https://doi.org/10.3390/cells11193150 - 7 Oct 2022
Cited by 8 | Viewed by 3109
Abstract
The concept of the tripartite synapse describes the close interaction of pre- and postsynaptic elements and the surrounding astrocyte processes. For glutamatergic synapses, it is established that the presence of astrocytic processes and their structural arrangements varies considerably between and within brain regions [...] Read more.
The concept of the tripartite synapse describes the close interaction of pre- and postsynaptic elements and the surrounding astrocyte processes. For glutamatergic synapses, it is established that the presence of astrocytic processes and their structural arrangements varies considerably between and within brain regions and between synapses of the same neuron. In contrast, less is known about the organization of astrocytic processes at GABAergic synapses although bi-directional signaling is known to exist at these synapses too. Therefore, we established super-resolution expansion microscopy of GABAergic synapses and nearby astrocytic processes in the stratum radiatum of the mouse hippocampal CA1 region. By visualizing the presynaptic vesicular GABA transporter and the postsynaptic clustering protein gephyrin, we documented the subsynaptic heterogeneity of GABAergic synaptic contacts. We then compared the volume distribution of astrocytic processes near GABAergic synapses between individual synapses and with glutamatergic synapses. We made two novel observations. First, astrocytic processes were more abundant at the GABAergic synapses with large postsynaptic gephyrin clusters. Second, astrocytic processes were less abundant in the vicinity of GABAergic synapses compared to glutamatergic, suggesting that the latter may be selectively approached by astrocytes. Because of the GABA transporter distribution, we also speculate that this specific arrangement enables more efficient re-uptake of GABA into presynaptic terminals. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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18 pages, 2442 KiB  
Article
Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes
by Tatiana Ilchibaeva, Anton Tsybko, Andre Zeug, Franziska E. Müller, Daria Guseva, Stephan Bischoff, Evgeni Ponimaskin and Vladimir Naumenko
Cells 2022, 11(15), 2384; https://doi.org/10.3390/cells11152384 - 2 Aug 2022
Cited by 9 | Viewed by 4077
Abstract
Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and [...] Read more.
Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT2A and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT2A may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT2A and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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17 pages, 3150 KiB  
Article
Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
by Patrícia M. Silva, Inês V. da Silva, Maria J. Sarmento, Ítala C. Silva, Filomena A. Carvalho, Graça Soveral and Nuno C. Santos
Cells 2022, 11(8), 1308; https://doi.org/10.3390/cells11081308 - 12 Apr 2022
Cited by 10 | Viewed by 2746
Abstract
Background: Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 [...] Read more.
Background: Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 involvement in cell biomechanical properties, cell–cell adhesion, and cell migration, following a loss-of-function strategy on BxPC-3 cells. Results: Silencing of AQP3 and AQP5 was functionally validated by reduced membrane permeability and had implications on cell migration, slowing wound recovery. Moreover, silenced AQP5 and AQP3/5 cells showed higher membrane fluidity. Biomechanical and morphological changes were assessed by atomic force microscopy (AFM), revealing AQP5 and AQP3/5 silenced cells with a lower stiffness than their control. Through cell–cell adhesion measurements, the work (energy) necessary to detach two cells was found to be lower for AQP-silenced cells than control, showing that these AQPs have implications on cell–cell adhesion. Conclusion: These findings highlight AQP3 and AQP5 involvement in the biophysical properties of cell membranes, whole cell biomechanical properties, and cell–cell adhesion, thus having potential implication in the settings of tumor development. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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14 pages, 24685 KiB  
Article
The Activation of GPR27 Increases Cytosolic L-Lactate in 3T3 Embryonic Cells and Astrocytes
by Dorian Dolanc, Tomaž M. Zorec, Zala Smole, Anja Maver, Anemari Horvat, Thanigaimalai Pillaiyar, Saša Trkov Bobnar, Nina Vardjan, Marko Kreft, Helena Haque Chowdhury and Robert Zorec
Cells 2022, 11(6), 1009; https://doi.org/10.3390/cells11061009 - 16 Mar 2022
Cited by 7 | Viewed by 3061
Abstract
G-protein-coupled receptors (GPCRs) represent a family with over 800 members in humans, and one-third of these are targets for approved drugs. A large number of GPCRs have unknown physiologic roles. Here, we investigated GPR27, an orphan GPCR belonging to the family of super [...] Read more.
G-protein-coupled receptors (GPCRs) represent a family with over 800 members in humans, and one-third of these are targets for approved drugs. A large number of GPCRs have unknown physiologic roles. Here, we investigated GPR27, an orphan GPCR belonging to the family of super conserved receptor expressed in the brain, with unknown functions. Cytosolic levels of L-lactate ([lactate]i), the end product of aerobic glycolysis, were measured with the Laconic fluorescence resonance energy transfer nanosensor. In single 3T3 wild-type (WT) embryonic cells, the application of 8535 (1 µM), a surrogate agonist known to activate GPR27, resulted in an increase in [lactate]i. Similarly, an increase was recorded in primary rat astrocytes, a type of neuroglial cell abundant in the brain, which contain glycogen and express enzymes of aerobic glycolysis. In CRISPR-Cas9 GPR27 knocked out 3T3 cells, the 8535-induced increase in [lactate]i was reduced compared with WT controls. Transfection of the GPR27-carrying plasmid into the 3T3KOGPR27 cells rescued the 8535-induced increase in [lactate]i. These results indicate that stimulation of GPR27 enhances aerobic glycolysis and L-lactate production in 3T3 cells and astrocytes. Interestingly, in the absence of GPR27 in 3T3 cells, resting [lactate]i was increased in comparison with controls, further supporting the view that GPR27 regulates L-lactate homeostasis. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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15 pages, 1693 KiB  
Article
3D In Vitro Platform for Cell and Explant Culture in Liquid-like Solids
by Duy T. Nguyen, Jack E. Famiglietti, Ryan A. Smolchek, Zadia Dupee, Nickolas Diodati, Diego I. Pedro, Juan M. Urueña, Matthew A. Schaller and W. Gregory Sawyer
Cells 2022, 11(6), 967; https://doi.org/10.3390/cells11060967 - 11 Mar 2022
Cited by 5 | Viewed by 4517
Abstract
Existing 3D cell models and technologies have offered tools to elevate cell culture to a more physiologically relevant dimension. One mechanism to maintain cells cultured in 3D is by means of perfusion. However, existing perfusion technologies for cell culture require complex electronic components, [...] Read more.
Existing 3D cell models and technologies have offered tools to elevate cell culture to a more physiologically relevant dimension. One mechanism to maintain cells cultured in 3D is by means of perfusion. However, existing perfusion technologies for cell culture require complex electronic components, intricate tubing networks, or specific laboratory protocols for each application. We have developed a cell culture platform that simply employs a pump-free suction device to enable controlled perfusion of cell culture media through a bed of granular microgels and removal of cell-secreted metabolic waste. We demonstrated the versatile application of the platform by culturing single cells and keeping tissue microexplants viable for an extended period. The human cardiomyocyte AC16 cell line cultured in our platform revealed rapid cellular spheroid formation after 48 h and ~90% viability by day 7. Notably, we were able to culture gut microexplants for more than 2 weeks as demonstrated by immunofluorescent viability assay and prolonged contractility. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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11 pages, 10013 KiB  
Article
Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor
by Laura Bizzozero, Margherita Pergolizzi, Davide Pascal, Elena Maldi, Giulia Villari, Jessica Erriquez, Marco Volante, Guido Serini, Caterina Marchiò, Federico Bussolino and Marco Arese
Cells 2022, 11(2), 280; https://doi.org/10.3390/cells11020280 - 14 Jan 2022
Cited by 7 | Viewed by 2328
Abstract
Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 [...] Read more.
Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor–nerve interactions, we assessed a potential NLGN1–GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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17 pages, 2992 KiB  
Article
The Cross-Talk between Myeloid and Mesenchymal Stem Cells of Human Bone Marrow Represents a Biomarker of Aging That Regulates Immune Response and Bone Reabsorption
by Maria Elisa Perico, Tommaso Maluta, Giamaica Conti, Antonio Vella, Lisa Provezza, Tiziana Cestari, Giulia De Cao, Lydia Segalla, Cristina Tecchio, Fabio Benedetti, Francesco Santini, Vincenzo Bronte, Bruno Magnan, Andrea Sbarbati and Dunia Ramarli
Cells 2022, 11(1), 1; https://doi.org/10.3390/cells11010001 - 21 Dec 2021
Cited by 4 | Viewed by 3240
Abstract
One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of [...] Read more.
One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of mesenchymal cells with other cells having the same embryological origin. Newly formed adipocytes were also observed in the trabecular matrix of elderly people’s bones, associated with myeloid cells. In this study, we have investigated the relationship between immature myeloid-derived suppressor cells (I-MDSCs) and mesenchymal stem cells (MSCs) in bone marrow (BM) samples harvested from 57 patients subjected to different orthopedic surgeries. Patients aged from 18 to 92 years were considered in order to compare the cellular composition of bone marrow of young and elderly people, considered a biomarker of immunity, inflammation, and bone preservation. The I-MDSC percentage was stable during aging, but in elderly people, it was possible to observe a strong basal immunosuppression of autologous and heterologous T cells’ proliferation. We hypothesized that this pattern observed in elders depends on the progressive accumulation in the BM of activating stimuli, including cell–cell contact, or the production of different cytokines and proteins that induce the differentiation of bone marrow mesenchymal stem cells in adipocytes. The collected data provided underline the importance of specific biomarkers of aging that promote a reduction in immune response and incremented inflammatory pathways, leading to bone reabsorption in elderly people. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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Review

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18 pages, 403 KiB  
Review
Astrocyte Heterogeneity in Regulation of Synaptic Activity
by Anna Kruyer
Cells 2022, 11(19), 3135; https://doi.org/10.3390/cells11193135 - 5 Oct 2022
Cited by 4 | Viewed by 2399
Abstract
Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity and specialization across brain regions. Whether all astrocytes are poised to signal in a multitude of ways, or are instead tuned to [...] Read more.
Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity and specialization across brain regions. Whether all astrocytes are poised to signal in a multitude of ways, or are instead tuned to surrounding synapses and how astroglial signaling is altered in psychiatric and cognitive disorders are fundamental questions for the field. In recent years, molecular and morphological characterization of astroglial types has broadened our ability to design studies to better analyze and manipulate specific functions of astroglia. Recent data emerging from these studies will be discussed in depth in this review. I also highlight remaining questions emerging from new techniques recently applied toward understanding the roles of astrocytes in synapse regulation in the adult brain. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
16 pages, 1055 KiB  
Review
A Special Network Comprised of Macrophages, Epithelial Cells, and Gut Microbiota for Gut Homeostasis
by Wei Chen, Dan Liu, Changhao Ren, Xiaomin Su, Chun-Kwok Wong and Rongcun Yang
Cells 2022, 11(2), 307; https://doi.org/10.3390/cells11020307 - 17 Jan 2022
Cited by 8 | Viewed by 3516
Abstract
A number of gut epithelial cells derived immunological factors such as cytokines and chemokines, which are stimulated by the gut microbiota, can regulate host immune responses to maintain a well-balance between gut microbes and host immune system. Multiple specialized immune cell populations, such [...] Read more.
A number of gut epithelial cells derived immunological factors such as cytokines and chemokines, which are stimulated by the gut microbiota, can regulate host immune responses to maintain a well-balance between gut microbes and host immune system. Multiple specialized immune cell populations, such as macrophages, dendritic cells (DCs), innate lymphoid cells, and T regulatory (Treg) cells, can communicate with intestinal epithelial cells (IEC) and/or the gut microbiota bi-directionally. The gut microbiota contributes to the differentiation and function of resident macrophages. Situated at the interface between the gut commensals and macrophages, the gut epithelium is crucial for gut homeostasis in microbial recognition, signaling transformation, and immune interactions, apart from being a physical barrier. Thus, three distinct but interactive components—macrophages, microbiota, and IEC—can form a network for the delicate and dynamic regulation of intestinal homeostasis. In this review, we will discuss the crucial features of gut microbiota, macrophages, and IEC. We will also summarize recent advances in understanding the cooperative and dynamic interactions among the gut microbiota, gut macrophages, and IEC, which constitute a special network for gut homeostasis. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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21 pages, 3271 KiB  
Review
The Blood–Brain Barrier, an Evolving Concept Based on Technological Advances and Cell–Cell Communications
by Camille Menaceur, Fabien Gosselet, Laurence Fenart and Julien Saint-Pol
Cells 2022, 11(1), 133; https://doi.org/10.3390/cells11010133 - 31 Dec 2021
Cited by 18 | Viewed by 3124
Abstract
The construction of the blood–brain barrier (BBB), which is a natural barrier for maintaining brain homeostasis, is the result of a meticulous organisation in space and time of cell–cell communication processes between the endothelial cells that carry the BBB phenotype, the brain pericytes, [...] Read more.
The construction of the blood–brain barrier (BBB), which is a natural barrier for maintaining brain homeostasis, is the result of a meticulous organisation in space and time of cell–cell communication processes between the endothelial cells that carry the BBB phenotype, the brain pericytes, the glial cells (mainly the astrocytes), and the neurons. The importance of these communications for the establishment, maturation and maintenance of this unique phenotype had already been suggested in the pioneering work to identify and demonstrate the BBB. As for the history of the BBB, the evolution of analytical techniques has allowed knowledge to evolve on the cell–cell communication pathways involved, as well as on the role played by the cells constituting the neurovascular unit in the maintenance of the BBB phenotype, and more particularly the brain pericytes. This review summarises the key points of the history of the BBB, from its origin to the current knowledge of its physiology, as well as the cell–cell communication pathways identified so far during its development, maintenance, and pathophysiological alteration. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Microenvironment)
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