scholarly journals Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Su-Jin Heo ◽  
Tristan P Driscoll ◽  
Stephen D Thorpe ◽  
Nandan L Nerurkar ◽  
Brendon M Baker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nuclear Architecture ◽  
Human Mscs ◽  
Nuclear Deformation ◽  
Biophysical Properties ◽  
Soluble Factors ◽  
Physical Cues ◽  
Differentiation Factors ◽  
Heterochromatin Content ◽  
Msc Differentiation

Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation-induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical-loading-induced calcium signaling and differentiated marker expression. This sensitization was reversed when the ‘stiff’ differentiated nucleus was softened and was enhanced when the ‘soft’ undifferentiated nucleus was stiffened through pharmacologic treatment. Interestingly, dynamic loading of undifferentiated MSCs, in the absence of soluble differentiation factors, stiffened and condensed the nucleus, and increased mechanosensitivity more rapidly than soluble factors. These data suggest that the nucleus acts as a mechanostat to modulate cellular mechanosensation during differentiation.

scholarly journals Atypical Mesenchymal Stromal Cell Responses to Topographic Modifications of Titanium Biomaterials Indicate Cytoskeletal- and Genetic Plasticity-Based Heterogeneity of Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Mohammad R. Khan ◽  
Nicola Mordan ◽  
Mohamed Parkar ◽  
Vehid Salih ◽  
Nikolaos Donos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Surface Modifications ◽  
Phenotypic Change ◽  
Surface Oxide Layer ◽  
Human Mscs ◽  
Morphological Adaptation ◽  
Soluble Factors ◽  
Stem Cell Pluripotency

Titanium (Ti) is widely used as a biomaterial for endosseous implants due to its relatively inert surface oxide layer that enables implanted devices the ability of assembling tissue reparative components that culminate in osseointegration. Topographic modifications in the form of micro- and nanoscaled structures significantly promote osseointegration and enhance the osteogenic differentiation of adult mesenchymal stromal cells (MSCs). While the biological mechanisms central to the differential responses of tissues and cells to Ti surface modifications remain unknown, adhesion and morphological adaptation are amongst the earliest events at the cell-biomaterial interface that are highly influenced by surface topography and profoundly impact the regulation of stem cell fate determination. This study correlated the effects of Ti topographic modifications on adhesion and morphological adaptation of human MSCs with phenotypic change. The results showed that modified Ti topographies precluded the adhesion of a subset of MSCs while incurring distinct morphological constraints on adherent cells. These effects anomalously corresponded with a differential expression of stem cell pluripotency and Wnt signalling-associated markers on both modified surfaces while additionally differing between hydrophobic and hydrophilic surface modifications—though extent of osteogenic differentiation induced by both modified topographies yielded similarly significant higher levels of cellular mineralisation in contrast to polished Ti. These results suggest that in the absence of deposited proteins and soluble factors, both modified topographies incur the selective adhesion of a subpopulation of progenitors with relatively higher cytoskeletal plasticity. While the presence of deposited proteins and soluble factors does not significantly affect adherence of cells, nanotopographic modifications enhance expression of pluripotency markers in proliferative conditions, which are conversely overridden by both modified topographies in osteogenic inductive conditions. Further deciphering the mechanisms underlying cellular selectivity and Ti topographic responsiveness will improve our understanding of stem cell heterogeneity and advance the potential of MSCs in regenerative medicine.

scholarly journals Gain of CXCR7 function with mesenchymal stem cell therapy ameliorates experimental arthritis via enhancing tissue regeneration and immunomodulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sung-Tai Wei ◽  
Yen-Chih Huang ◽  
Jung-Ying Chiang ◽  
Chia-Ching Lin ◽  
Yu-Jung Lin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Tissue Regeneration ◽  
Chondrogenic Differentiation ◽  
Human Mscs ◽  
Gain Of Function ◽  
Soluble Factors ◽  
Therapeutic Benefits ◽  
Anti Inflammatory

Abstract Background The major barriers to mesenchymal stem cell (MSC) therapy in rheumatoid arthritis (RA) are a low extent of tissue regeneration and insufficient immunomodulation after cell transplantation. In addition, the role of C-X-C chemokine receptor type 7 (CXCR7) and its mechanism of action in MSC-mediated osteogenic or chondrogenic differentiation and immunomodulation are unclear. Methods Gain of CXCR7 function on human MSCs was carried out by lentiviral vector-mediated CXCR7 overexpression or CXCR7 agonist, TC14012. These cells were determined the role and potential mechanisms for CXCR7-regulated MSC differentiation and immunomodulation using cellular and molecular assays. The therapeutic benefits in RA were investigated in rats with collagen-induced arthritis (CIA). Results CXCR7 was upregulated in MSCs during the induction of osteogenic or chondrogenic differentiation. Blockage of CXCR7 function inhibited osteogenic or chondrogenic differentiation of MSCs whereas gain of CXCR7 function had the opposite effects. Besides, MSCs with CXCR7 gain-of-function facilitated macrophage apoptosis and regulatory T cell differentiation in a co-culture system. Gain of CXCR7 function also promoted the production of anti-inflammatory soluble factors. A gene expression profiling assay and signaling reporter assays revealed that CXCR7 could regulate several candidate genes related to the PPAR, WNT, Hedgehog or Notch pathways, and their signaling activities, which are known to control cell differentiation and immunomodulation. Finally, MSCs with CXCR7 gain-of-function significantly reduced the articular index scores, ankle circumference, radiographic scores, histologic scores, and inflammation in rats with CIA compared with control MSCs. Conclusions CXCR7 promotes the osteogenic and chondrogenic differentiation of MSCs and MSC-mediated immunomodulation by regulating several signaling pathways and anti-inflammatory soluble factors. MSCs with CXCR7 gain-of-function significantly ameliorate arthritic symptoms in a CIA model.

Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Mesodermal Cell ◽  
Cell Lineages ◽  
Current Review ◽  
Differentiation Factors ◽  
The Relationship ◽  
Msc Differentiation

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Characterization of Gelatin Composite with Low Content Hydroxyapatite and the Influence on Mesenchymal Stem Cell Culture

2016 ◽  
Vol 675-676 ◽  
pp. 473-476 ◽  
Author(s):  
Junjira Tanum ◽  
Suruk Udomsom ◽  
Wassanai Wattanutchariya ◽  
Pat Sooksaen ◽  
Fahsai Kantawong
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Mscs ◽  
Natural Bone Mineral ◽  
Hydrogel Scaffolds ◽  
Force Microscopy ◽  
Adhesion Ability ◽  
Atomic Force ◽  
Nanocrystalline Hydroxyapatite ◽  
Composition And Structure

In tussue engineering, hydrogel-based scaffold is one of the most common method for bone tissue engineering. Gelatin is a common material for scaffold, whereas hydroxyapatite (HA) has a similar composition and structure to natural bone mineral. HA can also increase cell adhesion ability of the scaffold. This research focuses on the fabrication of hydrogel scaffolds using gelatin composite with nanocrystalline hydroxyapatite (nHA). Then the mechanical and physical caharacteristics of the scaffold is investigetad. Low contents nHA is introduced into gelatin in order to modulate mesenchymal stem cell (MSC) behavior. There are three types of scaffolds which contain various HA content. The gelatin is crosslinked with glutaraldehyde before freeze-drying. The Young’s modulus of the surface is investigated using Atomic force microscopy (AFM). The pore size is investigated using scanning electron microscope (SEM). Human MSCs are culture on the scaffold for 3 weeks. The result shows the sucesse in cell cultivation. However, the human MSCs cultured on the fabricated hydrogels do not show any lineage-specific differentiation.

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

2021 ◽  
Author(s):  
Ganesan Jothimani ◽  
Surajait Pathak ◽  
Suman Dutta ◽  
Asim K. Duttaroy ◽  
Antara Banerjee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Expression Patterns ◽  
Functional Enrichment ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

scholarly journals Quantitative Efficacy and Fate of Mesenchymal Stromal Cells Targeted to Cardiac Sites by Radiofrequency Catheter Ablation

2020 ◽  
Vol 29 ◽  
pp. 096368972091423
Author(s):  
Rizwan Malik ◽  
Fabrice F. Darche ◽  
Rasmus Rivinius ◽  
Anja Seckinger ◽  
Ulf Krause ◽  
...  
Keyword(s):  
Stem Cell ◽  
Catheter Ablation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Radiofrequency Catheter Ablation ◽  
Functional Integration ◽  
Right Atrial ◽  
Blue Staining ◽  
Large Animal ◽  
Human Mscs

Engraftment and functional integration of stem cells or stem cell-derived cells within cardiac tissue is an important prerequisite for cell replacement therapy aiming at the treatment of heart disease. Recently, a novel intravenous approach for application of mesenchymal stromal cells (MSCs) to cardiac sites has been established using radiofrequency catheter ablation (RFCA)-guided targeting, bypassing the need for open chest surgery or direct myocardial cell injection. However, little is known about the quantitative efficacy and longevity of this strategy. We performed selective power-controlled RFCA with eight ablation pulses (30 W, 60 s each) to induce heat-mediated lesions at the right atrial appendices (RAAs) of pigs. Different concentrations of human bone marrow-derived MSCs (105 to 1.6 × 106 cells/kg bodyweight) labeled with superparamagnetic iron oxide (SPIO) particles were infused intravenously in nine pigs one d after RFCA treatment and hearts were explanted 8 d later to quantify the number of engrafted cells. Prussian blue staining revealed high numbers of SPIO-labeled cells in areas surrounding the RFCA-induced lesions. Cell numbers were evaluated by quantitative real-time polymerase chain reaction using specific primers for human MSCs (hMSCs), which indicated that up to 106 hMSCs, corresponding to ∼3.9% of the systemically applied human cells, engrafted within the RAAs of RFCA-treated pigs. Of note, infused hMSCs were observed in nontargeted organs, as well, but appeared at very low concentrations. To assess long-term deposition of MSCs, RAAs of three pigs were analyzed after 6 months, which revealed few persisting hMSCs at targeted sites. RFCA-mediated targeting of MSCs provides a novel minimal invasive strategy for cardiac stem cell engraftment. Qualitative and quantitative results of our large animal experiments indicate an efficient guidance of MSCs to selected cardiac regions, although only few cells remained at targeted sites 6 mo after cell transplantation.

scholarly journals Role of mesenchymal stem cell-derived soluble factors and folic acid in wound healing

2019 ◽  
Vol 49 (3) ◽  
pp. 914-921 ◽  
Author(s):  
Ahu PAKDEMİRLİ ◽  
Feriha TOKSÖZ ◽  
Aslıhan KARADAĞ ◽  
Hüseyin Koray MISIRLIOĞLU ◽  
Yasemin BAŞBINAR ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Folic Acid ◽  
Mesenchymal Stem Cell ◽  
Soluble Factors

scholarly journals Control of Differentiation of Human Mesenchymal Stem Cells by Altering the Geometry of Nanofibers

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Satoshi Fujita ◽  
Harue Shimizu ◽  
Shin-ichiro Suye
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Clinical Applications ◽  
Soluble Factors ◽  
Precise Control ◽  
Mixed Medium ◽  
Aligned Nanofibers ◽  
Different Types ◽  
Msc Differentiation

Effective differentiation of mesenchymal stem cells (MSCs) is required for clinical applications. To control MSC differentiation, induction media containing different types of soluble factors have been used to date; however, it remains challenging to obtain a uniformly differentiated population of an appropriate quality for clinical application by this approach. We attempted to develop nanofiber scaffolds for effective MSC differentiation by mimicking anisotropy of the extracellular matrix structure, to assess whether differentiation of these cells can be controlled by using geometrically different scaffolds. We evaluated MSC differentiation on aligned and random nanofibers, fabricated by electrospinning. We found that induction of MSCs into adipocytes was markedly more inhibited on random nanofibers than on aligned nanofibers. In addition, adipoinduction on aligned nanofibers was also inhibited in the presence of mixed adipoinduction and osteoinduction medium, although osteoinduction was not affected by a change in scaffold geometry. Thus, we have achieved localized control over the direction of differentiation through changes in the alignment of the scaffold even in the presence of a mixed medium. These findings indicate that precise control of MSC differentiation can be attained by using scaffolds with different geometry, rather than by the conventional use of soluble factors in the medium.

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