scholarly journals Mechanism and Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells for the Treatment of Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingyi You ◽  
Zhou Fu ◽  
Lin Zou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Infectious Diseases ◽  
Extracellular Vesicles ◽  
Respiratory Infections ◽  
Tissue Injury ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Inflammatory Factors ◽  
Repair Tissue

Extracellular vesicles (EVs) are nano-sized membrane vesicles secreted by cells. EVs serve as a mediator for cell-to-cell communication by regulating the exchange of genetic materials and proteins between the donor and surrounding cells. Current studies have explored the therapeutic value of mesenchymal stem cells-derived EVs (MSC-EVs) for the treatment of infectious diseases extensively. MSC-EVs can eliminate the pathogen, regulate immunity, and repair tissue injury in contagious diseases through the secretion of antimicrobial factors, inhibiting the replication of pathogens and activating the phagocytic function of macrophages. MSC-EVs can also repair tissue damage associated with the infection by upregulating the levels of anti-inflammatory factors, downregulating the pro-inflammatory factors, and participating in the regulation of cellular biological behaviors. The purpose of this mini-review is to discuss in detail the various mechanisms of MSC-EV treatment for infectious diseases including respiratory infections, sepsis, and intestinal infections, as well as challenges for implementing MSC-EVs from bench to bedside.

scholarly journals Very Long-Chain C24:1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 37 ◽  
Author(s):  
Andrew Khayrullin ◽  
Priyanka Krishnan ◽  
Luis Martinez-Nater ◽  
Bharati Mendhe ◽  
Sadanand Fulzele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cardiovascular Health ◽  
Rhesus Macaques ◽  
Cell Communication ◽  
Size Exclusion ◽  
Target Cells ◽  
Serum Samples

Extracellular vesicles (EVs), including exosomes and microvesicles, function in cell-to-cell communication through delivery of proteins, lipids and microRNAs to target cells via endocytosis and membrane fusion. These vesicles are enriched in ceramide, a sphingolipid associated with the promotion of cell senescence and apoptosis. We investigated the ceramide profile of serum exosomes from young (24–40 yrs.) and older (75–90 yrs.) women and young (6–10 yrs.) and older (25–30 yrs.) rhesus macaques to define the role of circulating ceramides in the aging process. EVs were isolated using size-exclusion chromatography. Proteomic analysis was used to validate known exosome markers from Exocarta and nanoparticle tracking analysis used to characterize particle size and concentration. Specific ceramide species were identified with lipidomic analysis. Results show a significant increase in the average amount of C24:1 ceramide in EVs from older women (15.4 pmol/sample) compared to those from younger women (3.8 pmol/sample). Results were similar in non-human primate serum samples with increased amounts of C24:1 ceramide (9.3 pmol/sample) in older monkeys compared to the younger monkeys (1.8 pmol/sample). In vitro studies showed that primary bone-derived mesenchymal stem cells (BMSCs) readily endocytose serum EVs, and serum EVs loaded with C24:1 ceramide can induce BMSC senescence. Elevated ceramide levels have been associated with poor cardiovascular health and memory impairment in older adults. Our data suggest that circulating EVs carrying C24:1 ceramide may contribute directly to cell non-autonomous aging.

scholarly journals Alteration of payload in extracellular vesicles by crosstalk with mesenchymal stem cells from different origin

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dong Jun Park ◽  
Jeong-Eun Park ◽  
Tae Hoon Kong ◽  
Young Joon Seo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Damage ◽  
Recipient Cell ◽  
Amyloid Β ◽  
Inflammatory Factors ◽  
Target Disease ◽  
Human Middle Ear ◽  
Different Origins

Abstract Background The application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads. Results Here, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1β, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-β A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively. Conclusions In conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine. Graphical abstract

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles: Roles in Tumor Growth, Progression, and Drug Resistance

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoyan Zhang ◽  
Huaijun Tu ◽  
Yazhi Yang ◽  
Lijun Fang ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Messenger Rna ◽  
Drug Response ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Malignant Diseases ◽  
Tumor Diseases

Mesenchymal stem cells (MSCs) are ubiquitously present in many tissues. Due to their unique advantages, MSCs have been widely employed in clinical studies. Emerging evidences indicate that MSCs can also migrate to the tumor surrounding stroma and exert complex effects on tumor growth and progression. However, the effect of MSCs on tumor growth is still a matter of debate. Several studies have shown that MSCs could favor tumor growth. On the contrary, other groups have demonstrated that MSCs suppressed tumor progression. Extracellular vesicles have emerged as a new mechanism of cell-to-cell communication in the development of tumor diseases. MSCs-derived extracellular vesicles (MSC-EVs) could mimic the effects of the mesenchymal stem cells from which they originate. Different studies have reported that MSC-EVs may exert various effects on the growth, metastasis, and drug response of different tumor cells by transferring proteins, messenger RNA, and microRNA to recipient cells. In the present review, we summarize the components of MSC-EVs and discuss the roles of MSC-EVs in different malignant diseases, including the related mechanisms that may account for their therapeutic potential. MSC-EVs open up a promising opportunity in the treatment of cancer with increased efficacy.

scholarly journals The Role of Microvesicles Derived from Mesenchymal Stem Cells in Lung Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jie Chen ◽  
Chonghui Li ◽  
Liangan Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Messenger Rna ◽  
Lung Diseases ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Experimental Models

Microvesicles (MVs) are membrane vesicles that are released by many types of cells and have recently been considered important mediators of cell-to-cell communication. MVs serve as a vehicle to transfer proteins and messenger RNA and microRNA (miRNA) to distant cells, which alters the gene expression, proliferation, and differentiation of the recipient cells. Several studies have demonstrated that mesenchymal stem cells (MSCs) have the capacity to reverse acute and chronic lung injury in different experimental models through paracrine mechanisms. This paracrine action may be partially accounted for by MVs that are derived from MSCs. MSC-derived MVs may confer a stem cell-like phenotype to injured cells with the consequent activation of self-regenerative programmers. In this review, we summarize the characteristics and biological activities of MSC-derived MVs, and we describe their potential in novel therapeutic approaches in regenerative medicine to repair damaged tissues. Additionally, we provide an overview of studies that have assessed the role of MSC-derived MVs in lung diseases, including the mechanisms that may account for their therapeutic potential. Finally, we discuss the clinical use of MSC-derived MVs with several suggestions for enhancing their therapeutic efficiency.

scholarly journals Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Marta Garcia-Contreras ◽  
Avnesh S. Thakor
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Human Adipose Tissue ◽  
Microglial Cells ◽  
Human Microglia ◽  
Oxide Synthase

AbstractNeurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), are driven by neuroinflammation triggered by activated microglial cells; hence, the phenotypic regulation of these cells is an appealing target for intervention. Human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) may be a potential therapeutic candidate to treat NDs given their immunomodulatory properties. Evidence suggests that the mechanism of action of hAD-MSCs is through their secretome, which includes secreted factors such as cytokines, chemokines, or growth factors as well as extracellular vesicles (EVs). Recently, EVs have emerged as important mediators in cell communication given, they can transfer proteins, lipids, and RNA species (i.e., miRNA, mRNA, and tRNAs) to modulate recipient cells. However, the therapeutic potential of hAD-MSCs and their secreted EVs has not been fully elucidated with respect to human microglia. In this study, we determined the therapeutic potential of different hAD-MSCs doses (200,000, 100,000, and 50,000 cells) or their secreted EVs (50, 20, or 10 µg/ml), on human microglial cells (HMC3) that were activated by lipopolysaccharides (LPS). Upregulation of inducible nitric oxide synthase (iNOS), an activation marker of HMC3 cells, was prevented when they were cocultured with hAD-MSCs and EVs. Moreover, hAD-MSCs inhibited the secretion of proinflammatory factors, such as IL-6, IL-8, and MCP-1, while their secreted EVs promoted the expression of anti-inflammatory mediators such as IL-10 or TIMP-1 in activated microglia. The present data therefore support a role for hAD-MSCs and their secreted EVs, as potential therapeutic candidates for the treatment of NDs.

scholarly journals Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Xing ◽  
Shuang Han ◽  
Gu Cheng ◽  
Yifeng Ni ◽  
Zhi Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Proteomic Analysis ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Protein Profile ◽  
Cell Communication ◽  
Average Diameter ◽  
Target Cells ◽  
General Function

Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

Alteration of Payload in Extracellular Vesicles by Crosstalk With Mesenchymal Stem Cells From Different Origin

2021 ◽  
Author(s):  
Dong Jun Park ◽  
Jeong-Eun Park ◽  
Tae Hoon Kong ◽  
YoungJoon Seo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Damage ◽  
Recipient Cell ◽  
Amyloid Β ◽  
Inflammatory Factors ◽  
Target Disease ◽  
Human Middle Ear ◽  
Different Origins

Abstract BackgroundThe application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads.ResultsHere, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1β, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-β A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively.ConclusionsIn conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

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