Extracellular Microvesicles (MV’s) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells

AbstractExtracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action.

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Mesenchymal Stem Cells and Cancer: Clinical Challenges and Opportunities

BioMed Research International ◽

10.1155/2019/2820853 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 23

Author(s):

Weiping Lin ◽

Linfeng Huang ◽

Ying Li ◽

Bin Fang ◽

Gang Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Anticancer Agents ◽

Therapeutic Potential ◽

Current Knowledge ◽

Cell Types ◽

Inhibit Tumor Growth ◽

Challenges And Opportunities ◽

Promising Source ◽

Target Cancer

Stem cell-based therapies exhibit profound therapeutic potential for treating various human diseases, including cancer. Among the cell types that can be used for this purpose, mesenchymal stem cells (MSCs) are considered as promising source of stem cells in personalized cell-based therapies. The inherent tumor-tropic property of MSCs can be used to target cancer cells. Although the impacts of MSCs on tumor progression remain elusive, they have been genetically modified or engineered as targeted anticancer agents which could inhibit tumor growth by blocking different processes of tumor. In addition, there are close interactions between MSCs and cancer stem cells (CSCs). MSCs can regulate the growth of CSCs through paracrine mechanisms. This review aims to focus on the current knowledge about MSCs-based tumor therapies, the opportunities and challenges, as well as the prospective of its further clinical implications.

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The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review

Journal of Translational Medicine ◽

10.1186/s12967-019-02136-7 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 7

Author(s):

Soukaina Bahsoun ◽

Karen Coopman ◽

Elizabeth C. Akam

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cell Types ◽

Surface Marker Expression ◽

Wide Range ◽

And Migration ◽

The Impact

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.

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5-Azacytidine and Resveratrol Enhance Chondrogenic Differentiation of Metabolic Syndrome-Derived Mesenchymal Stem Cells by Modulating Autophagy

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1523140 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 4

Author(s):

K. Marycz ◽

J. M. Irwin Houston ◽

C. Weiss ◽

M. Röcken ◽

K. Kornicka

Keyword(s):

Metabolic Syndrome ◽

Stem Cells ◽

Chondrogenic Differentiation ◽

Therapeutic Potential ◽

Early Stage ◽

Mitochondrial Dynamics ◽

The Body ◽

Stem Cell Population ◽

Wide Range

Recently, metabolic syndrome (MS) has gained attention in human and animal metabolic medicine. Insulin resistance, inflammation, hyperleptinemia, and hyperinsulinemia are critical to its definition. MS is a complex cluster of metabolic risk factors that together exert a wide range of effects on multiple organs, tissues, and cells in the body. Adipose stem cells (ASCs) are multipotent stem cell population residing within the adipose tissue that is inflamed during MS. Studies have indicated that these cells lose their stemness and multipotency during MS, which strongly reduces their therapeutic potential. They suffer from oxidative stress, apoptosis, and mitochondrial deterioration. Thus, the aim of this study was to rejuvenate these cells in vitro in order to improve their chondrogenic differentiation effectiveness. Pharmacotherapy of ASCs was based on resveratrol and 5-azacytidine pretreatment. We evaluated whether those substances are able to reverse aged phenotype of metabolic syndrome-derived ASCs and improve their chondrogenic differentiation at its early stage using immunofluorescence, transmission and scanning electron microscopy, real-time PCR, and flow cytometry. Obtained results indicated that 5-azacytidine and resveratrol modulated mitochondrial dynamics, autophagy, and ER stress, leading to the enhancement of chondrogenesis in metabolically impaired ASCs. Therefore, pretreatment of these cells with 5-azacytidine and resveratrol may become a necessary intervention before clinical application of these cells in order to strengthen their multipotency and therapeutic potential.

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More to Explore; The Mesenchymal Stem Cells (MSCs) Major Tissue Sources, Known Surface Markers, and Its Immunomodulation properties

American Journal of Pure and Applied Biosciences ◽

10.34104/ajpab.021.085097 ◽

2021 ◽

pp. 85-97

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Modulation ◽

Molecular Mechanisms ◽

Cell Types ◽

Surface Markers ◽

Differentiation Potential ◽

Disease Therapy ◽

Multipotent Progenitor Cells ◽

Mesodermal Origin

Mesenchymal stem cells (MSCs) are currently available for a range of applications and have become a good material for regenerative medicine, tissue engineering, and disease therapy. MSCs are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into cell types of mesodermal origin, such as adipocytes, osteocytes, and chondrocytes, and exert potent immunosuppressive potentials. In the present review, we highlight the currently reported variations in the differentiation potential of MSCs from different tissue sources, the minimal criteria to define MSCs from various tissue environments, and provide a detailed description of MSCs surface markers. Furthermore, MSC's immunomodulatory features secrete cytokines and immune receptors which regulate the microenvironment in the host tissue also revisits in detail. We propose that there are likely more sources of MSCs waiting to be discovered. We need to Standardize MSCs characterization by selecting markers for isolation, cellular and molecular mechanisms involved in MSC-mediated immune modulation, and other functionalities of MSCs should be characterized prior to use in clinical applications.

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Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation

Cellular & Molecular Biology Letters ◽

10.2478/s11658-013-0083-2 ◽

2013 ◽

Vol 18 (2) ◽

Cited By ~ 16

Author(s):

Dana Foudah ◽

Juliana Redondo ◽

Cristina Caldara ◽

Fabrizio Carini ◽

Giovanni Tredici ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Neural Cells ◽

Human Mscs ◽

Differentiation Markers ◽

Neuronal Markers ◽

Wide Range

AbstractMesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into mesodermal lineages (osteogenic, adipogenic, chondrogenic), but also towards non-mesodermal derivatives (e.g. neural cells). Recent in vitro studies revealed that, in the absence of any kind of differentiation stimuli, undifferentiated MSCs express neural differentiation markers, but the literature data do not all concur. Considering their promising therapeutic potential for neurodegenerative diseases, it is very important to expand our knowledge about this particular biological property of MSCs. In this study, we confirmed the spontaneous expression of neural markers (neuronal, glial and progenitor markers) by undifferentiated human MSCs (hMSCs) and in particular, we demonstrated that the neuronal markers βIII-tubulin and NeuN are expressed by a very high percentage of hMSCs, regardless of the number of culture passages and the culture conditions. Moreover, the neuronal markers βIII-tubulin and NeuN are still expressed by hMSCs after in vitro osteogenic and adipogenic differentiation. On the other hand, chondrogenically differentiated hMSCs are negative for these markers. Our findings suggest that the expression of neuronal markers could be common to a wide range of cellular types and not exclusive for neuronal lineages. Therefore, the expression of neuronal markers alone is not sufficient to demonstrate the differentiation of MSCs towards the neuronal phenotype. Functional properties analysis is also required.

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Bone Anabolic Effects of Soluble Si:In VitroStudies with Human Mesenchymal Stem Cells and CD14+ Osteoclast Precursors

Stem Cells International ◽

10.1155/2016/5653275 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

J. Costa-Rodrigues ◽

S. Reis ◽

A. Castro ◽

M. H. Fernandes

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Plasma Levels ◽

Human Mesenchymal Stem Cells ◽

Cell Types ◽

Osteoclast Precursors ◽

Wide Range ◽

Basal Plasma ◽

Important Player ◽

And Function

Silicon (Si) is indispensable for many cellular processes including bone tissue metabolism. In this work, the effects of Si on human osteogenesis and osteoclastogenesis were characterized. Human mesenchymal stem cells (hMSC) and CD14+ stem cells, as osteoblast and osteoclast precursors, were treated with a wide range of Si concentrations, covering the physiological plasma levels. Si promoted a dose-dependent increase in hMSC proliferation, differentiation, and function, at levels similar to the normal basal plasma levels. Additionally, a decrease in the expression of the osteoclastogenic activators M-CSF and RANKL was observed. Also, Si elicited a decrease in osteoclastogenesis, which became significant at higher concentrations, as those observed after meals. Among the intracellular mechanisms studied, an upregulation of MEK and PKC signalling pathways was observed in both cell types. In conclusion, Si appears to have a direct positive effect on human osteogenesis, at basal plasma levels. On the other hand, it also seemed to be an inhibitor of osteoclastogenesis, but at higher concentrations, though yet in the physiological range. Further, an indirect effect of Si on osteoclastogenesis may also occur, through a downregulation of M-CSF and RANKL expression by osteoblasts. Thus, Si may be an important player in bone anabolic regenerative approaches.

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SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

BioMed Research International ◽

10.1155/2014/783459 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Botti Chiara ◽

Caiafa Ilaria ◽

Coppola Antonietta ◽

Cuomo Francesca ◽

Miceli Marco ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Human Mesenchymal Stem Cells ◽

Cell Types ◽

Therapeutic Angiogenesis ◽

Induced Response ◽

Human Mscs ◽

Hypoxic Conditions ◽

And Migration

Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types. Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders. However, the molecular mechanisms underlying these effects remain unclear. A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function. Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions. Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level. We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level. Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis. Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs. Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.

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Transcriptome Analysis of Long Noncoding RNAs in Toll-Like Receptor 3-Activated Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2016/6205485 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Shihua Wang ◽

Xiaoxia Li ◽

Robert Chunhua Zhao

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Length Distribution ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Therapeutic Effects ◽

Wide Range

Mesenchymal stem cells (MSCs) possess great immunomodulatory capacity which lays the foundation for their therapeutic effects in a variety of diseases. Recently, toll-like receptors (TLR) have been shown to modulate MSC functions; however, the underlying molecular mechanisms are poorly understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are an important class of regulators involved in a wide range of biological processes. To explore the potential involvement of lncRNAs in TLR stimulated MSCs, we performed a comprehensive lncRNA and mRNA profiling through microarray. 10.2% of lncRNAs (1733 out of 16967) and 15.1% of mRNA transcripts (1760 out of 11632) were significantly differentially expressed (absolute fold-change≥5 ,Pvalue≤0.05) in TLR3 stimulated MSCs. Furthermore, we characterized the differentially expressed lncRNAs through their classes and length distribution and correlated them with differentially expressed mRNA. Here, we are the first to determine genome-wide lncRNAs expression patterns in TLR3 stimulated MSCs by microarray and this work could provide a comprehensive framework of the transcriptome landscapes of TLR3 stimulated MSCs.

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Photobiomodulation of mineralisation in mesenchymal stem cells

Photochemical & Photobiological Sciences ◽

10.1007/s43630-021-00047-5 ◽

2021 ◽

Author(s):

Sherif A. Mohamad ◽

Michael R. Milward ◽

Mohammed A. Hadis ◽

Sarah A. Kuehne ◽

Paul R. Cooper

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Respiratory Chain ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Positive Effects ◽

Non Invasive ◽

Light Delivery ◽

Mineralisation Potential ◽

Respiratory Chain Activity

AbstractMesenchymal stem cells (MSCs) and photobiomodulation (PBM) both offer significant therapeutic potential in regenerative medicine. MSCs have the ability to self-renew and differentiate; giving rise to multiple cellular and tissue lineages that are utilised in repair and regeneration of damaged tissues. PBM utilises light energy delivered at a range of wavelengths to promote wound healing. The positive effects of light on MSC proliferation are well documented; and recently, several studies have determined the outcomes of PBM on mineralised tissue differentiation in MSC populations. As PBM effects are biphasic, it is important to understand the underlying cellular regulatory mechanisms, as well as, provide accurate details of the irradiation conditions, to optimise and standardise outcomes. This review article focuses on the use of red, near-infra-red (R/NIR) and blue wavelengths to promote the mineralisation potential of MSCs; and also reports on the possible molecular mechanisms which underpin transduction of these effects. A variety of potential photon absorbers have been identified which are reported to mediate the signalling mechanisms, including respiratory chain enzymes, flavins, and cryptochromes. Studies report that R/NIR and blue light stimulate MSC differentiation by enhancing respiratory chain activity and increasing reactive oxygen species levels; however, currently, there are considerable variations between irradiation parameters reported. We conclude that due to its non-invasive properties, PBM may, following optimisation, provide an efficient therapeutic approach to clinically support MSC-mediated hard tissue repair. However, to optimise application, further studies are required to identify appropriate light delivery parameters, as well as elucidate the photo-signalling mechanisms involved.

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Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with Light-Emitting Diode: Implications and Molecular Mechanisms

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6663539 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Barbara Sampaio Dias Martins Mansano ◽

Vitor Pocani da Rocha ◽

Ednei Luiz Antonio ◽

Daniele Fernanda Peron ◽

Rafael do Nascimento de Lima ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Protein Kinase ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Light Emitting Diode ◽

Janus Kinase ◽

Mitogen Activated Protein Kinase ◽

Light Emitting ◽

Report Quality

This study evaluated the effects of light-emitting diode (LED) on mesenchymal stem cells (MSCs). An electronic search was conducted in PubMed/MEDLINE, Scopus, and Web of Science database for articles published from 1980 to February 2020. Ten articles met the search criteria and were included in this review. The risk of bias was evaluated to report quality, safety, and environmental standards. MSCs were derived from adipose tissue, bone marrow, dental pulp, gingiva, and umbilical cord. Protocols for cellular irradiation used red and blue light spectrum with variations of the parameters. The LED has been shown to induce greater cellular viability, proliferation, differentiation, and secretion of growth factors. The set of information available leads to proposing a complex signaling cascade for the action of photobiomodulation, including angiogenic factors, singlet oxygen, mitogen-activated protein kinase/extracellular signal-regulated protein kinase, Janus kinase/signal transducer, and reactive oxygen species. In conclusion, although our results suggest that LED can boost MSCs, a nonuniformity in the experimental protocol, bias, and the limited number of studies reduces the power of systematic review. Further research is essential to find the optimal LED irradiation parameters to boost MSCs function and evaluate its impact in the clinical setting.

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