scholarly journals On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aliaksei S. Vasilevich ◽  
Steven Vermeulen ◽  
Marloes Kamphuis ◽  
Nadia Roumans ◽  
Said Eroumé ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Shape ◽  
Cell Function ◽  
Phenotypic Diversity ◽  
Human Mesenchymal Stem Cells ◽  
Early Response ◽  
Cell Physiology ◽  
Quantitative Image ◽  
Cell Shapes

Abstract Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

scholarly journals On the correlation between material-induced cell shape and phenotypical response of human mesenchymal stem cells

2020 ◽  
Author(s):  
Aliaksei S Vasilevich ◽  
Steven S Vermeulen ◽  
Marloes Kamphuis ◽  
Nadia Roumans ◽  
Said Eroume ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Shape ◽  
Cell Function ◽  
Phenotypic Diversity ◽  
Human Mesenchymal Stem Cells ◽  
Early Response ◽  
Cell Physiology ◽  
Cell Shapes ◽  
Open Question

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. Thus, we have started to unravel the open question of how cell function follows cell shape. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.

Human mesenchymal stem cells modulate B-cell functions

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 367-372 ◽  
Author(s):  
Anna Corcione ◽  
Federica Benvenuto ◽  
Elisa Ferretti ◽  
Debora Giunti ◽  
Valentina Cappiello ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Costimulatory Molecule ◽  
Human Mesenchymal Stem Cells ◽  
B Cell Differentiation ◽  
Major Mechanism ◽  
Cell Functions

Abstract Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.

scholarly journals ATF4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Daniel M Cohen ◽  
Kyoung-Jae Won ◽  
Nha Nguyen ◽  
Mitchell A Lazar ◽  
Christopher S Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Dna Sequence ◽  
Cell Shape ◽  
Chemical Cues ◽  
Adipocyte Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Seeding Density ◽  
Transcriptional Program

A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing transcription in human mesenchymal stem cells (hMSCs) adipogenically primed by confluence. Prior to adipogenesis, confluency promotes heterodimer recruitment of the bZip TFs C/EBPβ and ATF4 to a non-canonical C/EBP DNA sequence. ATF4 depletion decreases both cell-density-dependent transcription and adipocyte differentiation. Global profiling in hMSCs and a novel cell-free assay reveals that ATF4 requires C/EBPβ for genomic binding at a motif distinct from that bound by the C/EBPβ homodimer. Our observations demonstrate that C/EBPβ bridges the transcriptional programs in naïve, confluent cells and early differentiating pre-adipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPβ to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.

scholarly journals Enhancement of Mitochondrial Transfer by Antioxidants in Human Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chia-Jung Li ◽  
Po-Kong Chen ◽  
Li-Yi Sun ◽  
Cheng-Yoong Pang
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Human Mesenchymal Stem Cells ◽  
Cell Physiology ◽  
Fluorescence Confocal Microscopy ◽  
Coculture System ◽  
Mitochondrial Transfer

Excessive reactive oxygen species is the major component of a harsh microenvironment after ischemia/reperfusion injury in human tissues. Combined treatment of N-acetyl-L-cysteine (NAC) and L-ascorbic acid 2-phosphate (AAP) promoted the growth of human mesenchymal stem cells (hMSCs) and suppressed oxidative stress-induced cell death by enhancing mitochondrial integrity and function in vitro. In this study, we aimed to determine whether NAC and AAP (termed MCA) could enhance the therapeutic potential of hMSCs. We established a coculture system consisting of MCA-treated and H2O2-treated hMSCs and investigated the role of tunneling nanotubes (TNTs) in the exchange of mitochondria between the 2 cell populations. The consequences of mitochondria exchange were assessed by fluorescence confocal microscopy and flow cytometry. The results showed that MCA could increase the mitochondrial mass, respiratory capacity, and numbers of TNTs in hMSCs. The “energized” mitochondria were transferred to the injured hMSCs via TNTs, the oxidative stress was decreased, and the mitochondrial membrane potential of the H2O2-treated hMSCs was stabilized. The transfer of mitochondria decreased the expression of S616-phosphorylated dynamin-related protein 1, a protein that dictates the fragmentation/fission of mitochondria. Concurrently, MCA also enhanced mitophagy in the coculture system, implicating that damaged mitochondria were eliminated in order to maintain cell physiology.

Proliferation and multi-differentiation potentials of human mesenchymal stem cells on thermoresponsive PDMS surfaces grafted with PNIPAAm

2010 ◽  
Vol 30 (6) ◽  
pp. 455-455 ◽  
Author(s):  
Dongyan Shi ◽  
Dan Ma ◽  
Feiqing Dong ◽  
Chen Zong ◽  
Liyue Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

The Effect of Link N on the Differentiation of Human Mesenchymal Stem Cells

2012 ◽  
Vol 2 (1_suppl) ◽  
pp. s-0032-1320001-s-0032-1320001
Author(s):  
F. Mwale ◽  
H. T. Wang ◽  
L. Haglund ◽  
P. J. Roughley ◽  
J. Antoniou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells

Generation of human mesenchymal stem cells lacking diabetoporosity-associated miRNAs using CRISPR/Cas9

2020 ◽  
Author(s):  
I Foessl ◽  
A Groselj-Strele ◽  
JC Piswanger-Sölkner ◽  
H Dobnig ◽  
A Fahrleitner-Pammer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells
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