scholarly journals Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1605 ◽  
Author(s):  
Carl Randall Harrell ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Nebojsa Arsenijevic ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Bioactive Molecules ◽  
Therapeutic Effects

There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) that regulate phenotype, function and homing of immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for the therapeutic effects of MSC-EVs in attenuation of autoimmune and inflammatory diseases. We described the disease-specific cellular targets of MSC-EVs and defined MSC-sourced molecules, which were responsible for MSC-EV-based immunosuppression. Results obtained in a large number of experimental studies revealed that both local and systemic administration of MSC-EVs efficiently suppressed detrimental immune response in inflamed tissues and promoted survival and regeneration of injured parenchymal cells. MSC-EVs-based anti-inflammatory effects were relied on the delivery of immunoregulatory miRNAs and immunomodulatory proteins in inflammatory immune cells (M1 macrophages, dendritic cells (DCs), CD4+Th1 and Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 macrophages, tolerogenic DCs and T regulatory cells. Additionally, through the delivery of mRNAs and miRNAs, MSC-EVs activated autophagy and/or inhibited apoptosis, necrosis and oxidative stress in injured hepatocytes, neurons, retinal cells, lung, gut and renal epithelial cells, promoting their survival and regeneration.

The Molecular Mechanisms Through Which Placental Mesenchymal Stem Cell‐Derived Extracellular Vesicles Promote Myelin Regeneration

2022 ◽  
pp. 2101099
Author(s):  
Kaitlin C. Clark ◽  
David Wang ◽  
Priyadarsini Kumar ◽  
Sirjan Mor ◽  
Edwin Kulubya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms

scholarly journals Insights into the Effects of Mesenchymal Stem Cell-Derived Secretome in Parkinson’s Disease

2020 ◽  
Vol 21 (15) ◽  
pp. 5241 ◽  
Author(s):  
Michele d’Angelo ◽  
Annamaria Cimini ◽  
Vanessa Castelli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Neurotrophic Factors ◽  
Therapeutic Approach ◽  
Bioactive Molecules ◽  
Therapeutic Effects ◽  
Apoptotic Bodies ◽  
Neural Dysfunction

Mesenchymal stem cell (MSC)-derived secretome demonstrated therapeutic effects like those reported after MSCs transplantation. MSC-derived secretome may avoid various side effects of MSC-based therapy, comprising undesirable differentiation of engrafted MSCs and potential activation of the allogeneic immune response. MSC-derived secretome comprises soluble factors and encapsulated extravesicles (EVs). MSC-derived EVs comprise microvesicles, apoptotic bodies, and exosomes. In this review, we focus on the recent insights into the effects of MSC-derived secretome in Parkinson’s disease (PD). In particular, MSC-derived secretome and exosomal components counteracted neuroinflammation and enhanced antioxidant capacity and neurotrophic factors expression. In light of the insights reported in this review, MSC-derived secretome or their released exosomes may be used as a potential therapeutic approach or as adjuvant therapy to counteract the disease progression and improve PD symptoms. Also, MSC-derived secretome may be used as a vehicle in cell transplantation approaches to enhance the viability and survival of engrafted cells. Furthermore, since exosomes can cross the blood–brain barrier, they may be used as biomarkers of neural dysfunction. Further studies are necessary to fully characterize the bioactive molecules present in the secretome and to create a new, effective, cell-free therapeutic approach towards a robust clinical outcome for PD patients.

scholarly journals Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Yizhuo Wang ◽  
Meng Zhao ◽  
Shuyun Liu ◽  
Jun Guo ◽  
Yanrong Lu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Biological Function ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Bioactive Molecules ◽  
Live Cells ◽  
Therapeutic Effects ◽  
Innate Immune Cells ◽  
Beneficial Effects

Abstract Macrophages (Mφ) are primary innate immune cells that exhibit diverse functions in response to different pathogens or stimuli, and they are extensively involved in the pathology of various diseases. Extracellular vesicles (EVs) are small vesicles released by live cells. As vital messengers, macrophage-derived EVs (Mφ-EVs) can transfer multiple types of bioactive molecules from macrophages to recipient cells, modulating the biological function of recipient cells. In recent years, Mφ-EVs have emerged as vital mediators not only in the pathology of multiple diseases such as inflammatory diseases, fibrosis and cancers, but also as mediators of beneficial effects in immunoregulation, cancer therapy, infectious defense, and tissue repair. Although many investigations have been performed to explore the diverse functions of Mφ-EVs in disease pathology and intervention, few studies have comprehensively summarized their detailed biological roles as currently understood. In this review, we briefly introduced an overview of macrophage and EV biology, and primarily focusing on current findings and future perspectives with respect to the pathological and therapeutic effects of Mφ-EVs in various diseases.

scholarly journals Oct-4 Enhanced the Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Acute Kidney Injury

2020 ◽  
Vol 45 (1) ◽  
pp. 95-108 ◽  
Author(s):  
Zhi-Yuan  Zhang ◽  
Yan-Ping Hou ◽  
Xiang-Yu Zou ◽  
Xiao-Yu Xing ◽  
Guan-Qun Ju ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Nuclear Antigen ◽  
Vehicle Group ◽  
Tunel Staining ◽  
Therapeutic Effects

Background/Aims: Acute kidney injury (AKI) is a common clinical condition that can lead to chronic kidney failure. Although mesenchymal stem cell-derived extracellular vesicles (MSC EVs) are regarded as a potent AKI treatment, the mechanisms underlying their beneficial effects remain unclear. Oct-4 may play an important role in tissue injury repair. We thus hypothesized that oct-4 overexpression might enhance the therapeutic effects of MSC EVs in AKI treatment. Methods: Renal tubular epithelial cells were cultured in a low oxygen environment, then cocultured with MSC EVs or control medium for 48 h. BrdU and transferase-mediated dUTP nick-end labeling (TUNEL) staining were used to assess cell proliferation and apoptosis. Mice subjected to ischemia reperfusion were randomly divided into 4 groups, then injected with either phosphate-buffered saline (vehicle), EVs, EVs overexpressing oct-4 (EVs+Oct-4), and EVs not expressing Oct-4 (EVs–Oct-4). Blood creatinine (CREA) and urine nitrone levels were assessed 48 h and 2 weeks after injection. After ischemia reperfusion, renal tissues from each group were stained with TUNEL and proliferating cell nuclear antigen (PCNA) to determine the degree of apoptosis and proliferation. Masson trichrome staining was used to evaluate renal fibrosis progression. Snail gene expression was assessed using polymerase chain reaction (PCR). Results: At 48 h after hypoxic treatment, TUNEL and BrdU staining indicated that the EVs+Oct-4 group had the least apoptosis and the most proliferation, respectively. Treatment with EVs overexpressing Oct-4 significantly decreased serum Crea and blood urea nitrogen levels and rescued kidney fibrosis, as indicated by the low proportion of Masson staining, high number of PCNA-positive cells, and low number of TUNEL-positive cells. PCR analysis indicated that Snail was most upregulated in the vehicle group and least upregulated in the EVs+Oct-4 group. Conclusions: MSC EVs had a pronounced therapeutic effect on ischemic reperfusion injury-related AKI, and Oct-4 overexpression enhanced these therapeutic effects. Our results may inspire a new direction for AKI treatment with MSC EVs.

scholarly journals Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 467 ◽  
Author(s):  
Carl Harrell ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Nebojsa Arsenijevic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Genetic Material ◽  
Cell Number ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Tissue Repair And Regeneration

Mesenchymal stem cell (MSC)-sourced secretome, defined as the set of MSC-derived bioactive factors (soluble proteins, nucleic acids, lipids and extracellular vesicles), showed therapeutic effects similar to those observed after transplantation of MSCs. MSC-derived secretome may bypass many side effects of MSC-based therapy, including unwanted differentiation of engrafted MSCs. In contrast to MSCs which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions, including fulminant hepatitis, cerebral ischemia and myocardial infarction. Additionally, MSC-derived secretome could be massively produced from commercially available cell lines avoiding invasive cell collection procedure. In this review article we emphasized molecular and cellular mechanisms that were responsible for beneficial effects of MSC-derived secretomes in the treatment of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system. Results obtained in a large number of studies suggested that administration of MSC-derived secretomes represents a new, cell-free therapeutic approach for attenuation of inflammatory and degenerative diseases. Therapeutic effects of MSC-sourced secretomes relied on their capacity to deliver genetic material, growth and immunomodulatory factors to the target cells enabling activation of anti-apoptotic and pro-survival pathways that resulted in tissue repair and regeneration.

Mesenchymal Stem Cell Therapy for Oral Inflammatory Diseases: Research Progress and Future Perspectives

2020 ◽  
Vol 15 ◽  
Author(s):  
Wang Gong ◽  
Fei Wang ◽  
Yuqing He ◽  
Blake Heath ◽  
Xin Zeng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Immune Regulation ◽  
Tissue Damage ◽  
Inflammatory Diseases ◽  
Allergic Diseases ◽  
Research Progress ◽  
Epithelial Tissue ◽  
Oral Diseases ◽  
Mesenchymal Stem Cell Therapy

: Mesenchymal stem cell (MSC) therapy for clinical diseases associated with inflammation and tissue damage has become a progressive treatment strategy. MSCs have unique biological functions, such as homing, immune regulation, and differentiation capabilities, which provide the prerequisites for treatment of clinical diseases. Oral diseases are often associated with abnormal immune regulation and epithelial tissue damage. In this review, we summarize previous studies that use MSC therapy to treat various oral inflammatory diseases, including oral ulceration, allergic diseases, chemo/radiotherapy-induced oral mucositis, periodontitis, osteonecrosis of the jaw, Sjögren's syndrome (SS), among other similar diseases. We highlight MSC treatment as a promising approach in the management of oral inflammatory diseases, and discuss the obstacles that remain and must be overcome for MSC treatment to thrive in the future.

Sign in / Sign up

Export Citation Format

Share Document