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 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.

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.

scholarly journals Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
R. A. Contreras ◽  
F. E. Figueroa ◽  
F. Djouad ◽  
P. Luz-Crawford
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Multipotent Stem Cells ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studiedin vitroandin vivoin experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

scholarly journals Effect of Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells on Mice Infected with Prions

2009 ◽  
Vol 83 (11) ◽  
pp. 5918-5927 ◽  
Author(s):  
Chang-Hyun Song ◽  
Osamu Honmou ◽  
Natsuo Ohsawa ◽  
Kiminori Nakamura ◽  
Hirofumi Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Prion Diseases ◽  
Contralateral Side ◽  
Experimental Models ◽  
Brain Lesions ◽  
Trophic Factors ◽  
Human Mscs

ABSTRACT Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions in experimental models of ischemia, tumors, and neurodegenerative diseases and to ameliorate functional deficits. In this study, we attempted to evaluate the therapeutic potential of MSCs for treating prion diseases. Immortalized human MSCs (hMSCs) that express the LacZ gene were transplanted into the unilateral hippocampi or thalami of mice, and their distributions were monitored by the expression of β-galactosidase. In mice infected with prions, hMSCs transplanted at 120 days postinoculation (dpi) were detected on the contralateral side at 2 days after transplantation and existed there even at 3 weeks after transplantation. In contrast, few hMSCs were detected on the contralateral side for mock-infected mice. Interestingly, the migration of hMSCs appeared to correlate with the severity of neuropathological lesions, including disease-specific prion protein deposition. The hMSCs also migrated to a prion-specific lesion in the brain, even when intravenously injected. Although the effects were modest, intrahippocampal and intravenous transplantation of hMSCs prolonged the survival of mice infected with prions. A subpopulation of hMSCs in the brains of prion-infected mice produced various trophic factors and differentiated into cells of neuronal and glial lineages. These results suggest that MSCs have promise as a cellular vehicle for the delivery of therapeutic genes to brain lesions associated with prion diseases and, furthermore, that they may help to regenerate neuronal tissues damaged by prion propagation.

scholarly journals Extracellular Vesicles from Mesenchymal Stem Cells as Potential Treatments for Osteoarthritis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1287
Author(s):  
Nur Azira Mohd Noor ◽  
Asma Abdullah Nurul ◽  
Muhammad Rajaei Ahmad Mohd Zain ◽  
Wan Khairunnisaa Wan Nor Aduni ◽  
Maryam Azlan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Cartilage Regeneration ◽  
Target Cells ◽  
Inflammatory Drugs ◽  
Degenerative Disorder ◽  
Intercellular Communications

Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. There is little understanding of the cellular and molecular processes involved in pathophysiology of OA. Currently the treatment for OA is limited to painkillers and anti-inflammatory drugs, which only treat the symptoms. Some patients may also undergo surgical procedures to replace the damaged joints. Extracellular vesicles (EV) play an important role in intercellular communications and their concentration is elevated in the joints of OA patients, although their mechanism is unclear. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. In this review, we provide an overview of the current OA treatments and their limitations. We also discuss the role of EV in OA pathophysiology. Finally, we highlight the therapeutic potential of MSC-derived EV in OA and their challenges.

scholarly journals Cell Interplay in Osteoarthritis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zihao Li ◽  
Ziyu Huang ◽  
Lunhao Bai
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Synovial Fibroblasts ◽  
Health Concern ◽  
Common Chronic Disease ◽  
Cell Tissue ◽  
Induced Pluripotent

Osteoarthritis (OA) is a common chronic disease and a significant health concern that needs to be urgently solved. OA affects the cartilage and entire joint tissues, including the subchondral bone, synovium, and infrapatellar fat pads. The physiological and pathological changes in these tissues affect the occurrence and development of OA. Understanding complex crosstalk among different joint tissues and their roles in OA initiation and progression is critical in elucidating the pathogenic mechanism of OA. In this review, we begin with an overview of the role of chondrocytes, synovial cells (synovial fibroblasts and macrophages), mast cells, osteoblasts, osteoclasts, various stem cells, and engineered cells (induced pluripotent stem cells) in OA pathogenesis. Then, we discuss the various mechanisms by which these cells communicate, including paracrine signaling, local microenvironment, co-culture, extracellular vesicles (exosomes), and cell tissue engineering. We particularly focus on the therapeutic potential and clinical applications of stem cell-derived extracellular vesicles, which serve as modulators of cell-to-cell communication, in the field of regenerative medicine, such as cartilage repair. Finally, the challenges and limitations related to exosome-based treatment for OA are discussed. This article provides a comprehensive summary of key cells that might be targets of future therapies for OA.

Abstract P506: Sirt6 Overexpression Inhibits Senescence And Inflammation In Human Mesenchymal Stem Cells

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Rahul Neupane ◽  
Darukeshwara Joladarashi ◽  
Keith Youker ◽  
Muthu Kumar Krishnamoorthi ◽  
Arvind Bhimaraj ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Diabetic Patients ◽  
Human Mscs ◽  
Cell Based Therapy ◽  
Functional Efficiency ◽  
Genomics And Proteomics

Background: Mesenchymal Stem Cells (MSCs) offer regenerative and therapeutic potential in an injured tissue in diabetic conditions. But the functional efficiency of MSCs has been shown to decrease with diabetes and aging. This reduces the potential of cell-based therapy in diabetic patients. Recent studies have established the role of sirtuin family proteins in metabolic disease, inflammation, longevity, and DNA repair. However, their potential to be used as a therapeutic target in cardiomyopathy and heart failure remain unexplored. Objective: To investigate the role of Sirtuin 6 (SIRT6) in mesenchymal stem cells senescence and cardiac regeneration. Methods and Results: We performed genomics and proteomics in the human control and diabetic heart tissues collected from the heart transplant. Human MSCs were treated with high glucose and mouse MSCs were derived from the bone marrow of diabetic db/db mice for this study. We found that SIRT6 expression is reduced in the myocardium of diabetic patients compared to non-diabetic controls. The SIRT6 expression decreased in high glucose-treated human MSCs compared to mannitol-treated control MSCs as well as in db/db mice MSCs compared to control mice MSCs. These high glucose-treated human MSCs and db/db mice MSCs showed increased expression of senescence and inflammation-related markers like that in diabetic human myocardium. Furthermore, we used small interfering RNA (SIRT6-siRNA) in human MSCs to knock down the SIRT6 gene and validated our findings. Indeed, the knockdown of SIRT6 promoted senescence and inflammation in those MSCs. Finally, we used adeno-associated viruses (AAV-SIRT6) to overexpress SIRT6 in MSCs treated with high glucose and performed proteomic analysis. SIRT6 overexpression in high glucose-treated MSCs reduced the expression of senescence and inflammation related genes and proteins. Conclusion: Our results highlight the importance of SIRT6 in diabetic myocardium and its role in balancing senescence and inflammation in MSCs. The validation of such in vitro studies in a diabetic mouse model ( db/db ) along with transplantation of SIRT6 overexpressed db/db MSCs into the myocardium of diabetic mice could open doors to successfully use MSC therapy in diabetic patients in the future.

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 Therapeutic Potential of Mesenchymal Stem Cells and Their Products in Lung Diseases—Intravenous Administration versus Inhalation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 232
Author(s):  
Eleonore Fröhlich
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Lung Diseases ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Thrombus Formation ◽  
Pulmonary Vasculature ◽  
Target Cells ◽  
Treatment Protocols

The number of publications studying the therapeutic use of stem cells has steadily increased since 2000. Compared to other applications, there has been little interest in the evaluation of mesenchymal stem cells (MSCs) and MSC-derived products (mostly extracellular vesicles) for the treatment of respiratory diseases. Due to the lack of efficient treatments for acute respiratory distress syndrome caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the action of MSCs has also been studied. This review describes mode of action and use of MSCs and MSC-derived products in the treatment of lung diseases including the respective advantages and limitations of the products. Further, issues related to standardized production are addressed. Administration by inhalation of MSCs, compared to intravenous injection, could decrease cell damage by shear stress, eliminate the barrier to reach target cells in the alveoli, prevent thrombus formation in the pulmonary vasculature and retention in filter for extracorporeal membrane oxygenation. There is more feasible to deliver extracellular vesicles than MSCs with inhalers, offering the advantage of non-invasive and repeated administration by the patient. Major obstacles for comparison of results are heterogeneity of the products, differences in the treatment protocols and small study cohorts.

scholarly journals The Emerging Role of Exosomes in the Treatment of Human Disorders With a Special Focus on Mesenchymal Stem Cells-Derived Exosomes

2021 ◽  
Vol 9 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Vahid Niazi ◽  
Bashdar Mahmud Hussen ◽  
Mir Davood Omrani ◽  
Mohammad Taheri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Option ◽  
Cell Communication ◽  
Tumor Formation ◽  
Special Focus ◽  
Cell Proliferation And Differentiation ◽  
Cord Injury ◽  
Human Disorders

Extracellular vesicles (EVs) are produced by diverse eukaryotic and prokaryotic cells. They have prominent roles in the modulation of cell-cell communication, inflammation versus immunomodulation, carcinogenic processes, cell proliferation and differentiation, and tissue regeneration. These acellular vesicles are more promising than cellular methods because of the lower risk of tumor formation, autoimmune responses and toxic effects compared with cell therapy. Moreover, the small size and lower complexity of these vesicles compared with cells have made their production and storage easier than cellular methods. Exosomes originated from mesenchymal stem cells has also been introduced as therapeutic option for a number of human diseases. The current review aims at summarization of the role of EVs in the regenerative medicine with a focus on their therapeutic impacts in liver fibrosis, lung disorders, osteoarthritis, colitis, myocardial injury, spinal cord injury and retinal injury.

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