scholarly journals Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 474 ◽  
Author(s):  
Carl Randall Harrell ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Messenger Rna ◽  
Current Knowledge ◽  
Experimental Models ◽  
Bioactive Molecules ◽  
Therapeutic Effects ◽  
Degenerative Diseases ◽  
Cellular Mechanisms ◽  
Beneficial Effects ◽  
Cell Based Therapy ◽  
Parenchymal Cells

Mesenchymal stem cells (MSC) are, due to their immunosuppressive and regenerative properties, used as new therapeutic agents in cell-based therapy of inflammatory and degenerative diseases. A large number of experimental and clinical studies revealed that most of MSC-mediated beneficial effects were attributed to the effects of MSC-sourced exosomes (MSC-Exos). MSC-Exos are nano-sized extracellular vesicles that contain MSC-derived bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs)), enzymes, cytokines, chemokines, and growth factors) that modulate phenotype, function and homing of immune cells, and regulate survival and proliferation of parenchymal cells. In this review article, we emphasized current knowledge about molecular and cellular mechanisms that were responsible for MSC-Exos-based beneficial effects in experimental models and clinical trials. Additionally, we elaborated on the challenges of conventional MSC-Exos administration and proposed the use of new bioengineering and cellular modification techniques which could enhance therapeutic effects of MSC-Exos in alleviation of inflammatory and degenerative diseases.

scholarly journals Mini-Review: The Administration of Apoptotic Cells for Treating Rheumatoid Arthritis: Current Knowledge and Clinical Perspectives

2021 ◽  
Vol 12 ◽  
Author(s):  
Eric Toussirot ◽  
Francis Bonnefoy ◽  
Charline Vauchy ◽  
Sylvain Perruche ◽  
Philippe Saas
Keyword(s):  
Rheumatoid Arthritis ◽  
Hematopoietic Cell Transplantation ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Early Stage ◽  
Joint Inflammation ◽  
Experimental Models ◽  
Therapeutic Effects ◽  
Apoptotic Cells ◽  
Cell Based Therapy

Rheumatoid arthritis (RA) is a chronic immune-mediated disease managed by conventional synthetic drugs, such as methotrexate (MTX), and targeted drugs including biological agents. Cell-based therapeutic approaches are currently developed in RA, mainly mesenchymal stroma cell-based approaches. Early-stage apoptotic cells possess direct and indirect anti-inflammatory properties. During the elimination of dying cells (a process called efferocytosis), specific mechanisms operate to control immune responses. There are compelling evidences in experimental models of arthritis indicating that apoptotic cell administration may benefit joint inflammation, and may even have therapeutic effects on arthritis. Additionally, it has been demonstrated that apoptotic cells could be administered with standard treatments of RA, such as MTX or TNF inhibitors (TNFi), given even a synergistic response with TNFi. Interestingly, apoptotic cell infusion has been successfully experienced to prevent acute graft-vs.-host disease after hematopoietic cell transplantation in patients with hematologic malignancies, with a good safety profile. In this mini-review, the apoptotic cell-based therapy development in arthritis is discussed, as well as its transfer in the short-term to an innovative treatment for patients with RA. The use of apoptotic cell-derived factors, including secretome or phosphatidylserine-containing liposomes, in RA are also discussed.

scholarly journals From the Basis of Epimorphic Regeneration to Enhanced Regenerative Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Béryl Laplace-Builhé ◽  
Sarah Bahraoui ◽  
Christian Jorgensen ◽  
Farida Djouad
Keyword(s):  
Lessons Learned ◽  
Therapeutic Effects ◽  
Degenerative Diseases ◽  
Beneficial Effects ◽  
Knee Oa ◽  
Cellular Events ◽  
Current Cell ◽  
Improved Outcomes ◽  
Progenitor Cell Proliferation ◽  
Regenerative Therapies

Current cell-based therapies to treat degenerative diseases such as osteoarthritis (OA) fail to offer long-term beneficial effects. The therapeutic effects provided by mesenchymal stem cell (MSC) injection, characterized by reduced pain and an improved functional activity in patients with knee OA, are reported at short-term follow-up since the improved outcomes plateau or, even worse, decline several months after MSC administration. This review tackles the limitations of MSC-based therapy for degenerative diseases and highlights the lessons learned from regenerative species to comprehend the coordination of molecular and cellular events critical for complex regeneration processes. We discuss how MSC injection generates a positive cascade of events resulting in a long-lasting systemic immune regulation with limited beneficial effects on tissue regeneration while in regenerative species fine-tuned inflammation is required for progenitor cell proliferation, differentiation, and regeneration. Finally, we stress the direct or indirect involvement of neural crest derived cells (NCC) in most if not all adult regenerative models studied so far. This review underlines the regenerative potential of NCC and the limitations of MSC-based therapy to open new avenues for the treatment of degenerative diseases such as OA.

scholarly journals Stem/Progenitor Cells, Atherosclerosis and Cardiovascular Regeneration

2010 ◽  
Vol 4 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Olena Dotsenko
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Current Knowledge ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Trafficking ◽  
Chronic Coronary Artery Disease ◽  
Atherosclerosis Progression ◽  
Cell Based Therapy

Regenerative cell based therapy has potential to become effective adjuvant treatment for patients with atherosclerotic disease. Although data from animal studies support this notion, clinical studies undertaken in patients with acute and chronic coronary artery disease do not conclusively demonstrate benefits of such therapy. There are many questions on the stem cell translational roadmap. The basic mechanisms of stem cell-dependent tissue regeneration are not well understood. There is a debate regarding characterization of specific cell types conferring therapeutic effects. In particular, the role of endothelial progenitor cells as a specific reparative cell subtype is questioned, and the role of myeloid cell linage in fostering of vasculo- and angiogenesis is being increasingly appreciated. Intense discussions surround the place of stem/progenitor cells in atherosclerosis progression, plaque destabilization and vessel remodeling. This paper summarizes the current knowledge on the regenerative stem/progenitor cell definitions, mechanisms of stem cell trafficking, homing and their involvement in atherosclerosis progression.

scholarly journals Mitochondrial donation in translational medicine; from imagination to reality

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hesam Saghaei Bagheri ◽  
Farhad Bani ◽  
Savas Tasoglu ◽  
Amir Zarebkohan ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Translational Medicine ◽  
Specific Activity ◽  
Current Knowledge ◽  
Review Article ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Cellular Mechanisms ◽  
Pathological Conditions ◽  
Mitochondrial Transfer ◽  
Mitochondrial Donation

Abstract The existence of active crosstalk between cells in a paracrine and juxtacrine manner dictates specific activity under physiological and pathological conditions. Upon juxtacrine interaction between the cells, various types of signaling molecules and organelles are regularly transmitted in response to changes in the microenvironment. To date, it has been well-established that numerous parallel cellular mechanisms participate in the mitochondrial transfer to modulate metabolic needs in the target cells. Since the conception of stem cells activity in the restoration of tissues’ function, it has been elucidated that these cells possess a unique capacity to deliver the mitochondrial package to the juxtaposed cells. The existence of mitochondrial donation potentiates the capacity of modulation in the distinct cells to achieve better therapeutic effects. This review article aims to scrutinize the current knowledge regarding the stem cell’s mitochondrial transfer capacity and their regenerative potential.

scholarly journals Quercetin Impact in Pancreatic Cancer: An Overview on Its Therapeutic Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Parina Asgharian ◽  
Abbas Pirpour Tazehkand ◽  
Saiedeh Razi Soofiyani ◽  
Kamran Hosseini ◽  
Miquel Martorell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Bioactive Molecules ◽  
High Rate ◽  
Therapeutic Effects ◽  
Molecular Signaling ◽  
Anticancer Compounds ◽  
Beneficial Effects ◽  
Cancerous Cell ◽  
Alternative Drug ◽  
Advanced Stages

Pancreatic cancer (PC) is a lethal malignancy cancer, and its mortality rates have been increasing worldwide. Diagnosis of this cancer is complicated, as it does not often present symptoms, and most patients present an irremediable tumor having a 5-year survival rate after diagnosis. Regarding treatment, many concerns have also been raised, as most tumors are found at advanced stages. At present, anticancer compounds-rich foods have been utilized to control PC. Among such bioactive molecules, flavonoid compounds have shown excellent anticancer abilities, such as quercetin, which has been used as an adjunctive or alternative drug to PC treatment by inhibitory or stimulatory biological mechanisms including autophagy, apoptosis, cell growth reduction or inhibition, EMT, oxidative stress, and enhancing sensitivity to chemotherapy agents. The recognition that this natural product has beneficial effects on cancer treatment has boosted the researchers’ interest towards more extensive studies to use herbal medicine for anticancer purposes. In addition, due to the expensive cost and high rate of side effects of anticancer drugs, attempts have been made to use quercetin but also other flavonoids for preventing and treating PC. Based on related studies, it has been found that the quercetin compound has significant effect on cancerous cell lines as well as animal models. Therefore, it can be used as a supplementary drug to treat a variety of cancers, particularly pancreatic cancer. This review is aimed at discussing the therapeutic effects of quercetin by targeting the molecular signaling pathway and identifying antigrowth, cell proliferation, antioxidative stress, EMT, induction of apoptotic, and autophagic features.

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.

scholarly journals Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Adaze Bijou Enogieru ◽  
William Haylett ◽  
Donavon Charles Hiss ◽  
Soraya Bardien ◽  
Okobi Eko Ekpo
Keyword(s):  
Therapeutic Potential ◽  
Current Knowledge ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Experimental Models ◽  
Mitogen Activated Protein Kinase ◽  
Antioxidant Enzyme Activities ◽  
Beneficial Effects ◽  
Wide Range ◽  
Mitogen Activated Protein

A wide range of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion diseases, share common mechanisms such as neuronal loss, apoptosis, mitochondrial dysfunction, oxidative stress, and inflammation. Intervention strategies using plant-derived bioactive compounds have been offered as a form of treatment for these debilitating conditions, as there are currently no remedies to prevent, reverse, or halt the progression of neuronal loss. Rutin, a glycoside of the flavonoid quercetin, is found in many plants and fruits, especially buckwheat, apricots, cherries, grapes, grapefruit, plums, and oranges. Pharmacological studies have reported the beneficial effects of rutin in many disease conditions, and its therapeutic potential in several models of NDs has created considerable excitement. Here, we have summarized the current knowledge on the neuroprotective mechanisms of rutin in various experimental models of NDs. The mechanisms of action reviewed in this article include reduction of proinflammatory cytokines, improved antioxidant enzyme activities, activation of the mitogen-activated protein kinase cascade, downregulation of mRNA expression of PD-linked and proapoptotic genes, upregulation of the ion transport and antiapoptotic genes, and restoration of the activities of mitochondrial complex enzymes. Taken together, these findings suggest that rutin may be a promising neuroprotective compound for the treatment of NDs.

Role of stem-cell-derived microvesicles in the paracrine action of stem cells

2013 ◽  
Vol 41 (1) ◽  
pp. 283-287 ◽  
Author(s):  
Giovanni Camussi ◽  
Maria Chiara Deregibus ◽  
Vincenzo Cantaluppi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Biological Activities ◽  
Biological Action ◽  
Experimental Models ◽  
Specific Information ◽  
Cell Of Origin ◽  
Bioactive Lipids ◽  
Beneficial Effects ◽  
Cell Based Therapy

The paracrine theory has recently changed the view of the biological action of stem cells and of the subsequent potential application of stem cells in regenerative medicine. Indeed, most of the beneficial effects of stem-cell-based therapy have been attributed to soluble factors released from stem cells. In this context, MVs (microvesicles) released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, may play a relevant role in the intercellular communication between stem and injured cells. By transferring proteins, bioactive lipids, mRNA and microRNA, MVs act as vehicles of information that may lead to alteration of the phenotype of recipient cells. The exchange of information between stem cells and tissue-injured cells is reciprocal. The MV-mediated transfer of tissue-specific information from the injured cells to stem cells may reprogramme the latter to gain phenotypic and functional characteristics of the cell of origin. On the other hand, MVs released from stem cells may confer a stem-cell-like phenotype to injured cells, with the consequent activation of self-regenerative programmes. In fact, MVs released from stem cells retain several biological activities that are able to reproduce the beneficial effects of stem cells in a variety of experimental models.

scholarly journals Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Gihyun Lee ◽  
Hyunsu Bae
Keyword(s):  
Current Knowledge ◽  
Medicinal Herbs ◽  
Current Therapy ◽  
Psychiatric Disease ◽  
Therapeutic Effects ◽  
Complementary Method ◽  
Beneficial Effects ◽  
Symptoms Of Depression ◽  
Therapeutic Benefits ◽  
Life Threatening

Background. Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose. One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections. There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion. Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies.

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.

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