scholarly journals Histone deacetylase inhibitor overrides the effect of soft hydrogel on the mechanoresponse of human mesenchymal stem cells

2022 ◽  
Author(s):  
Rohit Joshi ◽  
Pooja Murlidharan ◽  
Puspendra Yadav ◽  
Vedanshi Dharnidharka ◽  
Abhijit Majumder
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Mapk Pathway ◽  
Chromatin Condensation ◽  
Chemical Stimulus ◽  
Differentiation Potential ◽  
Deacetylase Inhibitor

Human Mesenchymal cells (hMSCs) are promising in regenerative medicine for their multi-lineage differentiation capability. It has been demonstrated that lineage specification is governed by both chemical and mechanical cues. Among all the different mechanical cues known to control hMSCs fate, substrate stiffness is the most well-studied. It has been shown that the naive mesenchymal stem cells when cultured on soft gel, they commit towards adipogenic lineage while when cultured on stiff gel they become osteogenic. Soft substrates also cause less cell spreading, less traction, less focal adhesion assembly and stress fibre formation. Furthermore, chromatin condensation increases when cells are cultured on soft substrates. As the nucleus has been postulated to be mechanosensor and mechanotransducer, in this paper we asked the question how mechanosensing and mechanoresponse process will be influenced if we change the chromatin condensation by using an external chemical stimulus. To address this question, we treated hMSCs cultured on soft polyacrylamide (PA) gels with a histone deacetylase inhibitor (HDACi) called Valproic Acid (VA) which decondense the chromatin by hyperacetylation of histone proteins. We found that the treatment with VA overrides the effect of soft substrates on hMSCs morphology, cellular traction, nuclear localization of mechnosensory protein YAP, and differentiation. VA treated cells behaved as if they are on stiff substrates in all aspects tested here. Furthermore, we have shown that VA controls hMSCs differentiation via activation of ERK/MAPK pathway by increasing the p-ERK expression which inhibits adipogenic differentiation potential of mesenchymal stem cells. Collectively, these findings for the first time demonstrate that inhibiting histone acetylation can override the mechanoresponse of hMSCs. This work will help us to fundamentally understand the mechanosignalling process and to control the hMSCs differentiation in tissue engineering and regenerative medicine.

Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

Drug Research ◽  
2018 ◽  
Vol 68 (08) ◽  
pp. 450-456 ◽  
Author(s):  
Leila Mousazadeh ◽  
Effat Alizadeh ◽  
Nosratollah Zarghami ◽  
Shahryar Hashemzadeh ◽  
Sedigheh Aval ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Ex Vivo ◽  
Osteogenic Potential ◽  
Differentiation Potential ◽  
Deacetylase Inhibitor

Abstract Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression

2020 ◽  
Vol 28 (1) ◽  
pp. 283-302
Author(s):  
Dandan Zhang ◽  
Ni Ni ◽  
Yuyao Wang ◽  
Zhimin Tang ◽  
Huiqin Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Osteogenic Differentiation ◽  
Progenitor Cell ◽  
Bone Repair ◽  
Circular Rnas ◽  
Mineral Density ◽  
Differentiation Potential ◽  
Integrin Α5

AbstractAdipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.

scholarly journals Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

2018 ◽  
Vol 18 (3) ◽  
pp. 264 ◽  
Author(s):  
Roberto Berebichez-Fridman ◽  
Pablo R. Montero-Olvera
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Clinical Applications ◽  
The Body ◽  
Differentiation Potential ◽  
Advantages And Disadvantages

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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