scholarly journals Non-Coding RNAs Steering the Senescence-Related Progress, Properties, and Application of Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Jingyi Cai ◽  
Hexu Qi ◽  
Ke Yao ◽  
Yang Yao ◽  
Dian Jing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cellular Senescence ◽  
The Other ◽  
Skeletal System ◽  
Self Renewal ◽  
Regulatory Processes ◽  
Age Related ◽  
Non Coding Rnas

The thirst to postpone and even reverse aging progress has never been quenched after all these decades. Unequivocally, mesenchymal stem cells (MSCs), with extraordinary abilities such as self-renewal and multi-directional differentiation, deserve the limelight in this topic. Though having several affable clinical traits, MSCs going through senescence would, on one hand, contribute to age-related diseases and, on the other hand, lead to compromised or even counterproductive therapeutical outcomes. Notably, increasing evidence suggests that non-coding RNAs (ncRNAs) could invigorate various regulatory processes. With even a slight dip or an uptick of expression, ncRNAs would make a dent in or even overturn cellular fate. Thereby, a systematic illustration of ncRNAs identified so far to steer MSCs during senescence is axiomatically an urgent need. In this review, we introduce the general properties and mechanisms of senescence and its relationship with MSCs and illustrate the ncRNAs playing a role in the cellular senescence of MSCs. It is then followed by the elucidation of ncRNAs embodied in extracellular vesicles connecting senescent MSCs with other cells and diversified processes in and beyond the skeletal system. Last, we provide a glimpse into the clinical methodologies of ncRNA-based therapies in MSC-related fields. Hopefully, the intricate relationship between senescence and MSCs will be revealed one day and our work could be a crucial stepping-stone toward that future.

scholarly journals Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3367
Author(s):  
Rocío Mato-Basalo ◽  
Miriam Morente-López ◽  
Onno J Arntz ◽  
Fons A. J. van de Loo ◽  
Juan Fafián-Labora ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Cellular Senescence ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Age Related ◽  
Small Molecular Inhibitors

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.

scholarly journals Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vuong Cat Khanh ◽  
Toshiharu Yamashita ◽  
Kinuko Ohneda ◽  
Chiho Tokunaga ◽  
Hideyuki Kato ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cellular Senescence ◽  
Skin Flap ◽  
Reactive Oxygen ◽  
Oxygen Species

Abstract Aging induces numerous cellular disorders, such as the elevation of reactive oxygen species (ROS), in a number type of cells, including mesenchymal stem cells (MSCs). However, the correlation of ROS and impaired healing abilities as well as whether or not the inhibition of elevating ROS results in the rejuvenation of elderly MSCs is unclear. The rejuvenation of aged MSCs has thus recently received attention in the field of regenerative medicine. Specifically, extracellular vesicles (EVs) act as a novel tool for stem cell rejuvenation due to their gene transfer ability with systemic effects and safety. In the present study, we examined the roles of aging-associated ROS in the function and rejuvenation of elderly MSCs by infant EVs. The data clearly showed that elderly MSCs exhibited the downregulation of superoxide dismutase (SOD)1 and SOD3, which resulted in the elevation of ROS and downregulation of the MEK/ERK pathways, which are involved in the impairment of the MSCs’ ability to decrease necrotic area in the skin flap model. Furthermore, treatment with the antioxidant Edaravone or co-overexpression of SOD1 and SOD3 rescued elderly MSCs from the elevation of ROS and cellular senescence, thereby improving their functions. Of note, infant MSC-derived EVs rejuvenated elderly MSCs by inhibiting ROS production and the acceleration of cellular senescence and promoting the proliferation and in vivo functions in both type 1 and type 2 diabetic mice.

New insights into skin stem cell aging and cancer

2014 ◽  
Vol 42 (3) ◽  
pp. 663-669 ◽  
Author(s):  
M. Carmen Ortells ◽  
William M. Keyes
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Aging ◽  
Adult Tissue ◽  
Self Renewal ◽  
Tissue Specific ◽  
Regulatory Processes ◽  
Age Related ◽  
Stem Cell Aging ◽  
Growth Properties

Adult tissue homoeostasis requires continual replacement of cells that are lost due to normal turnover, injury and disease. However, aging is associated with an overall decline in tissue function and homoeostasis, suggesting that the normal regulatory processes that govern self-renewal and regeneration may become impaired with age. Tissue-specific SCs (stem cells) lie at the apex of organismal conservation and regeneration, ultimately being responsible for continued tissue maintenance. In many tissues, there are changes in SC numbers, or alteration of their growth properties during aging, often involving imbalances in tumour-suppressor- and oncogene-mediated pathways. Uncovering the molecular mechanisms leading to changes in SC function during aging will provide an essential tool to address tissue-specific age-related pathologies. In the present review, we summarize the age-related alterations found in different tissue SC populations, highlighting recently identified changes in aged HFSCs (hair-follicle SCs) in the skin.

Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow–derived mesenchymal stem cells and slow age-related degeneration

2021 ◽  
Vol 13 (578) ◽  
pp. eaaz8697
Author(s):  
Qian Lei ◽  
Fei Gao ◽  
Teng Liu ◽  
Wenxiang Ren ◽  
Li Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Nuclear Antigen ◽  
Aging Intervention ◽  
Age Related ◽  
Therapeutic Context ◽  
Proliferating Cell ◽  
Adult Bone

Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs). These UC-produced MSC-EVs (UC-EVs) contain abundant anti-aging signals and rejuvenate senescing adult bone marrow–derived MSCs (AB-MSCs). UC-EV–rejuvenated AB-MSCs exhibited alleviated aging phenotypes and increased self-renewal capacity and telomere length. Mechanistically, UC-EVs rejuvenate AB-MSCs at least partially by transferring proliferating cell nuclear antigen (PCNA) into recipient AB-MSCs. When tested in therapeutic context, UC-EV–triggered rejuvenation enhanced the regenerative capacities of AB-MSCs in bone formation, wound healing, and angiogenesis. Intravenously injected UC-EVs conferred anti-aging phenotypes including decreased bone and kidney degeneration in aged mice. Our findings reveal that UC-EVs are of high translational value in anti-aging intervention.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration

2020 ◽  
Vol 29 ◽  
pp. 096368972090850 ◽  
Author(s):  
Bocheng Zhang ◽  
Xiaoyuan Tian ◽  
Jun Hao ◽  
Gang Xu ◽  
Weiguo Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Membrane Structure ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Self Renewal ◽  
Multipotent Stem Cells

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.

scholarly journals Effect of lentivirus-mediated growth and differentiation factor-5 transfection on differentiation of rabbit nucleus pulposus mesenchymal stem cells

2020 ◽  
Author(s):  
Kun Zhu ◽  
Rui Zhao ◽  
Yuchen Ye ◽  
Gang Xu ◽  
Changchun Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Lentiviral Vector ◽  
The Other ◽  
Nucleus Pulposus Cells ◽  
Disc Disease ◽  
Qrt Pcr ◽  
Differentiation Factor ◽  
Age Related

Abstract Background：Intervertebral disc degeneration (IDD) is a natural progression of age-related process. Degenerative disc disease (DDD) is a pathologic condition associated with IDD that has been one of the most common causes of chronic low back pain, which can have a severe impact on patients’ quality of life. The purpose of this study is to observe the biological and cytological characteristics of rabbit nucleus pulposus mesenchymal stem cells (NPMSCs), and to determine the effect of growth and differentiation factor-5 (GDF-5) on the differentiation of rabbit NPMSCs transducted with lentivirus vector.Methods: In vitro culture model of rabbit NPMSCs was established and NPMSCs were identified by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Subsequently, NPMSCs were randomly divided into three groups: the lentiviral vector carrying GDF-5 gene used to transfect NPMSCs was recorded as transfection group; the NPMSCs transfected with an ordinary lentiviral vector was recorded as control virus group; the NPMSCs alone was normal group. FCM, qRT-PCR and Western Blot (WB) were used to detect the change of NPMSCs.Results: The transfected NPMSCs by GDF-5 gene displayed elongated shape, the cell density decreased, and the positive rate of GDF-5 in the transfected group was significantly higher than that in the other two groups (P < 0.05). The mRNA expression of KRT8, KRT18, and KRT19 in the transfected group was significantly higher in comparison with the other two groups (P < 0.05), and the result of WB was consistent with that of qRT-PCR.Conclusions: GDF-5 can induce the differentiation of NPMSCs and repair degenerative intervertebral disc. Lentiviral vector carrying GDF-5 gene can be integrated into the chromosome genome of NPMSCs and promote differentiation of NPMSCs into nucleus pulposus cells (NPCs).

Inhibition of cellular senescence by developmentally regulated FGF receptors in mesenchymal stem cells

Blood ◽  
2011 ◽  
Vol 117 (25) ◽  
pp. 6801-6812 ◽  
Author(s):  
Daniel L. Coutu ◽  
Moïra François ◽  
Jacques Galipeau
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Senescence ◽  
Bone Development ◽  
Fibroblast Growth Factors ◽  
Developmentally Regulated ◽  
Self Renewal ◽  
Mesenchymal Progenitors

Abstract Bone-derived mesenchymal stem cells (MSCs) are important cells for use in cell therapy, tissue engineering, and regenerative medicine, but also to study bone development, homeostasis, and repair. However, little is known about their developmental ontology and in vivo identity. Because fibroblast growth factors (FGFs) play key roles in bone development and their receptors are developmentally regulated in bones, we hypothesized that MSCs should express FGF receptors (FGFRs), reflecting their developmental origin and potential. We show here that FGFR1/2 are expressed by rare mesenchymal progenitors in putative MSC niches in vivo, including the perichondrium, periosteum, and trabecular marrow. FGFR1+ cells often appeared as pericytes. These cells display a characteristic MSC phenotype in vitro when expanded with FGF-2, which appears to maintain MSC stemness by inhibiting cellular senescence through a PI3K/AKT-MDM2 pathway and by promoting proliferation. FGFRs may therefore be involved in MSC self-renewal. In summary, FGFR1/2 are developmentally regulated markers of MSCs in vivo and in vitro and are important in maintaining MSC stemness.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Adult Stem Cells ◽  
Heart Diseases ◽  
Therapeutic Option ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

scholarly journals Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 667
Author(s):  
Gabriella Racchetti ◽  
Jacopo Meldolesi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Immune Regulation ◽  
Great Increase ◽  
The Body ◽  
Cell Aging ◽  
Therapeutic Effects ◽  
Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

scholarly journals Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor 4 ◽  
Anti Inflammatory ◽  
Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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