Role Of Mesenchymal Stem Cells Research Articles

The Role of Mesenchymal Stem Cells and Exosomes in Tumor Development and Targeted Antitumor Therapies.

Mesenchymal stem cells (MSCs) can be isolated from various tissues in adults and differentiated into cells of the osteoblasts, adipocytes, chondrocytes, and myocytes. Recruitments of MSCs towards tumors have a crucial contribution to tumor development. However, the role of MSCs in the tumor microenvironment is uncertain. In addition, due to its tropism to the tumor and low immunogenic properties, more and more pieces of evidence indicate that MSCs may be an ideal carrier for antitumor biologics such as cytokines, chemotherapeutic agents, and oncolytic viruses. Here, we review the existing knowledge on the anti- and protumorigenic effect of MSCs and their extracellular vesicles and exosomes, the role of MSCs, and their extracellular vesicles and exosomes as antitumor vectors.

Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

Mesenchymal stem cell-derived extracellular vesicles transfer miR-598 to inhibit the growth and metastasis of non-small-cell lung cancer by targeting THBS2

Non-small-cell lung cancer (NSCLC) is the subtype of lung cancer, which accounts for about 85% of diagnosed lung cancer cases, and is without any effective therapy. Emerging evidence has revealed microRNA-598 (miR-598) as potential therapeutic target and diagnostic marker of NSCLC. In the present study, we sought to define the role of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) containing miR-598 in NSCLC. Co-culture experiments were conducted to examine the secretion of miR-598 by MSCs and the uptake of EVs by NSCLC cells. The expression of miR-598 in NSCLC cell lines, tissues, and MSC-derived EVs was detected by the RT-qPCR. After treatment with MSCs-EVs, CCK-8 and Transwell assays were adopted to evaluate the effects of miR-598 on proliferation, migration, and invasion capacities of NSCLC cells. Finally, the effects of miR-598 on tumor growth and metastasis were further validated in vivo through subcutaneous tumorigenesis and experimental pulmonary metastasis in nude mice. We found that MSCs-derived EVs could deliver miR-598 into NSCLC cells, where miR-598 specifically targeted and bound with mRNA of THBS2 to inhibit its translational process. By suppressing the promoting effects of THBS2 on the proliferation, migration, and invasion of NSCLC cells, the EV treatment reduced the progression of NSCLC. Notably, these inhibitory effects were reversed by concomitantly overexpressing THBS2. Overall, we find that MSCs-derived EVs containing miR-598 targets THBS2 to inhibit the proliferation and migration of NSCLC cells in vivo and in vitro.

The Role of Mesenchymal Stem Cells in Modulating the Breast Cancer Microenvironment.

The role of mesenchymal stem cells (MSCs) in the breast tumor microenvironment (TME) is significant and multifaceted. MSCs are recruited to breast tumor sites through molecular signals released by tumor sites. Once in the TME, MSCs undergo polarization and interact with various cell populations, including immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), and breast cancer cells. In most cases, MSCs play roles in breast cancer therapeutic resistance, but there is also evidence that indicates their abilities to sensitize cancer cells to chemotherapy and radiotherapy. MSCs possess inherent regenerative and homing properties, making them attractive candidates for cell-based therapies. Therefore, MSCs can be engineered to express therapeutic molecules or deliver anti-cancer agents directly to tumor sites. Unraveling the intricate relationship between MSCs and the breast TME has the potential to uncover novel therapeutic targets and advance our understanding of breast cancer biology.

Role of Mesenchymal Stem Cells on Tonsillar Hypertrophy: An Unexplored Enigma.

interleukin-4; mesenchymal stem cell; tonsillar hypertrophy.

Advances in Understanding the Roles of Mesenchymal Stem Cells in Lung Cancer.

Lung cancer is the most common and deadliest type of cancer worldwide. Research concerning lung cancer has made considerable progress in recent decades, but lung cancer remains the leading cause of malignancy-related mortality rate. Mesenchymal stem cells (MSCs) mainly exist in fat, umbilical cord blood, bone marrow, bone, and muscle. MSCs are a primary component of the tumor microenvironment (TME). Recent studies have shown that MSCs have roles in lung cancer-related proliferation, invasion, migration, and angiogenesis, but the underlying mechanisms are poorly understood. Because MSCs can migrate to the TME, there is increasing attention toward the use of MSCs in drugs or gene vectors for cancer treatment. This review summarizes the roles and effects of MSCs in lung cancer, while addressing clinical applications of MSCs in lung cancer treatment.

The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines

We aimed to explain the role of mesenchymal stem cells (MSC-exosomes) on gene expressions of epithelial to mesenchymal transition (EMT), angiogenesis, and apoptosis. Four different cell lines were employed, including ACHN, 5637, LNCaP, and PC3, as well-known representatives for renal, bladder, hormone-sensitive, and hormone-refractory prostate cancers, respectively. Cell lines were exposed to diverse concentrations of mesenchymal stem cells-derived exosomes to find IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining. Micro Culture Tetrazolium Test assessed proliferative inhibitory effect; and prostate biomarker (KLK2), EMT (E-cadherin and Snail), angiogenesis genes (VEGF-A/VEGF-C), apoptosis genes (BAX/BCL2, P53) and Osteopontin variants (OPNa/b, and c) mRNA levels were studied by realtime PCR method. All 5637, LNCaP, and PC3 following treatment with exosomes illustrated specific responses with changes in expression of different genes. The increased TP53 and decreased BCL2 expressions were seen in 5637, LNCaP, and PC3. In PC3, OPNb and OPNc have raised more than P53; in LNCap, the increase was in VEGF-c. In 5637 cells, more than TP53 and BCL2 changes, two other genes, VEGFa and B.A.X., have decreased, suggesting exosomes’ anti-apoptotic and anti-angiogenic effects. The kidney tumor cell line saw no significant gene expression change in ten targeted genes. MSC-exosomes therapy has augmented some interesting antitumor effects on prostate, bladder, and kidney cancer cell lines. This effect which originates from exosomes’ potency to persuade apoptosis and prevent the proliferation of cancer cells simultaneously, was more substantial in bladder cancer, moderate in prostate cancer, and mild in renal cancer.

The Immunomodulatory Potential Role of Mesenchymal Stem Cells in Diseases of the Central Nervous System

Introduction: Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases. Methods: PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review. Results: This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously. Conclusion: It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.

Positive Aspects, Negative Aspects and Challenges Associated with Stem Cell Therapy for COVID - 19: A Mini-review.

Like any other pandemic, Covid-19 scenario has also demanded effective treatment options. The circumstances demand to utilize all the possible weapons in the armamentarium. There have been many issues regarding the short-term and long-term safety and efficacy of these options. Some options are like uncharted seas and these need a detailed and critical review with respect to safety, efficacy, feasibility and financial constraints. Mesenchymal stem cells (MSCs) therapy has been studied for many years for its potential role in diseases with complex pathogenesis. Its efficacy in controlling cytokine imbalance and immuno-modulatory properties is well proven. These effects are being extensively studied for potential extension of the benefits for an effective option for management of COVID-19 patients with severe respiratory involvement. In this mini-review, an attempt has been made to review positive aspects, negative aspects, and challenges influencing MSCs therapy in the management of COVID-19 disease. The results of various studies and literature reviews show that MSCs therapy can be considered as one of the potential options. This article reviews the role of Mesenchymal Stem Cell (MSC) transplantation in critically ill SARS-COV-19 patients with lung involvement. The MSCs counteract the cytokine storm, regulate the immune responses, facilitate the expression of essential growth factors, and eventually improve the local milieu and promote the restoration of pulmonary vascular and alveolar linings for early healing. As with all new therapeutic options, MSC therapy will also have to stand the test of time with respect to safety, specificity, and constraints like mass production and "available for all" at "affordable cost."

Role of Mesenchymal Stem Cells and Their Paracrine Mediators in Macrophage Polarization: An Approach to Reduce Inflammation in Osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration of the cartilage, bone remodeling, formation of osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium is the primary site of inflammation in OA and is frequently characterized by hyperplasia of the synovial lining and infiltration of inflammatory cells, primarily macrophages. Macrophages play a crucial role in the early inflammatory response through the production of several inflammatory cytokines, chemokines, growth factors, and proteinases. These pro-inflammatory mediators are activators of numerous signaling pathways that trigger other cytokines to further recruit more macrophages to the joint, ultimately leading to pain and disease progression. Very few therapeutic alternatives are available for treating inflammation in OA due to the condition's low self-healing capacity and the lack of clear diagnostic biomarkers. In this review, we opted to explore the immunomodulatory properties of mesenchymal stem cells (MSCs) and their paracrine mediators-dependent as a therapeutic intervention for OA, with a primary focus on the practicality of polarizing macrophages as suppression of M1 macrophages and enhancement of M2 macrophages can significantly reduce OA symptoms.

Mesenchymal Stem Cells Role in COVID-19 Myocardial Injury

Coronavirus Disease-19 (COVID-19) has become a global pandemic that affected the lives of billion individuals. The clinical spectrum of the disease varies from asymptomatic form to severe manifestation in term of acute respiratory distress syndrome (ARDS), shock and septic shock and multiple organ dysfunction syndrome (MODS). Clinical studies have also reported an association between COVID-19 and cardiovascular manifestation, such as myocardial injury, arrhythmias, acute coronary syndrome (ACS) and thromboembolism. Myocardial injury has been reported frequently and is associated with high mortality. The currently approved strategies for COVID-19 are supportive rather than curative treatment. Cell-based approaches, primarily using mesenchymal stem cell (MSC) has demonstrated safety and possible efficacy as an adjuvant therapy in COVID-19 patient. Mesenchymal stem cells have shown important role in the therapy of cardiovascular disease due to their prominent features including their ability to differentiate into cardiovascular cells, immunomodulatory properties, antifibrotic activity and ability to undergo neovasculogenic.

Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues implies a critical role for mesenchymal stem cells

SUMMARYExercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given the challenge of profiling heterogeneous effects across multiple tissues and cell types. Here, we address this challenge and opposing effects of exercise and high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous and visceral white adipose tissue and skeletal muscle in mice with diet and exercise training interventions. We identify a prominent role of mesenchymal stem cells (MSCs) in obesity and exercise-induced tissue adaptation. Among the pathways regulated by exercise and HFD in MSCs across the three tissues, extracellular matrix remodeling and circadian rhythm are the most prominent. Inferred cell-cell interactions implicate within- and multi-tissue crosstalk centered around MSCs. Overall, our work reveals the intricacies and diversity of multi-tissue molecular responses to exercise and obesity and uncovers a previously underappreciated role of MSCs in tissue-specific and multi-tissue beneficial effects of exercise.

Role of Mesenchymal Stem Cells and Extracellular Vesicles in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic disease that leads to disability and death within 5 years of diagnosis. Pulmonary fibrosis is a disease with a multifactorial etiology. The concept of aberrant regeneration of the pulmonary epithelium reveals the pathogenesis of IPF, according to which repeated damage and death of alveolar epithelial cells is the main mechanism leading to the development of progressive IPF. Cell death provokes the migration, proliferation and activation of fibroblasts, which overproduce extracellular matrix, resulting in fibrotic deformity of the lung tissue. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis. MSCs, and EVs derived from MSCs, modulate the activity of immune cells, inhibit the expression of profibrotic genes, reduce collagen deposition and promote the repair of damaged lung tissue. This review considers the molecular mechanisms of the development of IPF and the multifaceted role of MSCs in the therapy of IPF. Currently, EVs-MSCs are regarded as a promising cell-free therapy tool, so in this review we discuss the results available to date of the use of EVs-MSCs for lung tissue repair.

Human umbilical cord mesenchymal stem cell-derived exosomes promote neurological function recovery in rat after traumatic brain injury by inhibiting the activation of microglia and astrocyte.

Traumatic brain injury (TBI) is a serious neurological disorder with increasing worldwide incidence. Emerging evidence has shown a significant therapeutic role of mesenchymal stem cells (MSCs) derived exosomes on traumatic brain injury with broad application prospects as a cell-free therapy. However, a comprehensive understanding of its underlying mechanism remained elusive. In this study, umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes (UC-MSCs-Exo) were isolated by ultracentrifugation and injected intraventricularly in a rat model of TBI. Our results showed that UC-MSCs-Exo promoted functional recovery and reduced neuronal apoptosis in TBI rats. Moreover, UC-MSCs-Exo inhibited the activation of microglia and astrocytes during brain injury, thereby promoting functional recovery. However, the effect of UC-MSCs-Exo on the content of plasma inflammatory factors in rats was not significant. Collectively our study suggested that UC-MSCs-Exo promotes the recovery of neurological function in TBI rats by inhibiting the activation of microglia and astrocytes, providing a theoretical basis for new therapeutic strategies for central nervous system diseases.

A potential role of mesenchymal stem cells derived from human umbilical cord blood in ameliorating psoriasis-like skin lesion in the rats.

Psoriasis is a common autoimmune inflammatory skin disease, with no clear cause, treated with topical agents and phototherapy, conventional immunosuppressant drugs and biologic agents. Stem cell therapy has generated significant interest in regenerative medicine. The aim of this study was to use mesenchymal stem cell (MSC) therapy compared to the topical application of the standard conventional corticosteroid cream. Forty male adult albino rats were used, divided into four groups, 10 rats each: group I (control), group II (psoriasis-like lesions induced by usage of Aldara cream), group III (treated with betamethasone) and group IV (treated with MSCs). Specimens were stained with haematoxylin and eosin, Masson's trichrome, immune-histochemical technique for CD4, CD8 and CD31. Ultra-sections were prepared for transmission electron microscope (TEM) examination. Mesenchymal stem cells demonstrated efficacy in reduction of disease severity in the form of uniform epidermal thickness covered by a very thin keratin layer. Normally arranged layers of epidermal layers, with a clear border demarcation, were seen between the epidermis and the dermis with apparently intact basement membrane. TEM showed absence of gaps between the tightly connected cells of the basal layer and the resting basement membrane. Application of MSCs raises hope for developing a new, safe and effective therapy for psoriatic patients, avoiding the side effects of betamethasone.

Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues infers a critical role for mesenchymal stem cells

Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues infers a critical role for mesenchymal stem cells

Pathophysiology of Sepsis and Genesis of Septic Shock: The Critical Role of Mesenchymal Stem Cells (MSCs).

The treatment of sepsis and septic shock remains a major public health issue due to the associated morbidity and mortality. Despite an improvement in the understanding of the physiological and pathological mechanisms underlying its genesis and a growing number of studies exploring an even higher range of targeted therapies, no significant clinical progress has emerged in the past decade. In this context, mesenchymal stem cells (MSCs) appear more and more as an attractive approach for cell therapy both in experimental and clinical models. Pre-clinical data suggest a cornerstone role of these cells and their secretome in the control of the host immune response. Host-derived factors released from infected cells (i.e., alarmins, HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (e.g., LPS, peptidoglycans) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of cytokines/chemokines and growth factors that influence, respectively, immune cell recruitment and stem cell mobilization. However, the way in which MSCs exert their beneficial effects in terms of survival and control of inflammation in septic states remains unclear. This review presents the interactions identified between MSCs and mediators of immunity and tissue repair in sepsis. We also propose paradigms related to the plausible roles of MSCs in the process of sepsis and septic shock. Finally, we offer a presentation of experimental and clinical studies and open the way to innovative avenues of research involving MSCs from a prognostic, diagnostic, and therapeutic point of view in sepsis.

Study on Toxic Effects of Lead Acetate on Haematological Parameters of Adult Albino Rats and The Role of Mesenchymal Stem Cells and Flax Seeds Oil as Therapeutic Agents

Study on Toxic Effects of Lead Acetate on Haematological Parameters of Adult Albino Rats and The Role of Mesenchymal Stem Cells and Flax Seeds Oil as Therapeutic Agents

The pathological and therapeutic roles of mesenchymal stem cells in preeclampsia.

Mesenchymal stem cells (MSCs) have made progress in the treatment of ischemic and inflammatory diseases. Preeclampsia (PE) is characterized by placenta ischemic and inflammatory injury. Our paper summarized the new role of MSCs in PE pathology and its potency in PE therapy and analyzed its current limitations. Intravenously administered MSCs dominantly distributed in perinatal tissues. There may be additional advantages to using MSCs-based therapies for reproductive disorders. It will provide new ideas for future research in this field.

The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is a chronic disease characterized by inadequate or absent insulin production due to the autoimmune destruction of beta (β) cells in the pancreas. It was once called "juvenile diabetes" since the disease frequently occurs in children, but it can also develop in adults. According to the International Diabetes Federation, an estimated 700 million adults will suffer from diabetes by 2045. Although the exact cause of diabetes remains unknown, it is hypothesized that genetic factors, environmental factors, and exposure to certain viruses play a role in the development of T1D. To date, exogenous insulin is the most common treatment for T1D. However, it is not a cure for the disease. Islet cell transplantation and pancreatic transplantation are two additional treatments that have gained popularity in recent years, but their clinical application may be limited by the need for high doses of immunosuppressants, the rarity of human cadaveric islets, and the need for extensive surgery in pancreatic transplantation. Mesenchymal stem cells (MSCs) are a highly promising novel treatment for T1D and their discovery has advanced biological sciences by allowing for modification of cell fate and the development of higher-order cellular structures. They play an essential role in lowering levels of fasting blood sugar, hemoglobin A1c, and C-peptide, and in treating microvascular complications associated with T1D. However, some of the disadvantages of its use in clinical practice are limited to its method of collection, proliferation rate, cell activity with age, and the risk of tumour formation identified in some studies. Large-scale studies are required to discover the mechanism of action of MSCs after administration as well as the optimal route, dose, and timing to maximize the benefits to patients. This article focuses primarily on the role of MSCs in the treatment of T1D and compares the feasibility, benefits, and drawbacks of MSCs in the treatment of T1D.