Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

2021 ◽  
Vol 16 ◽  
Author(s):  
Lina María González ◽  
Laura Natalia Ospina ◽  
Laura Elena Sperling ◽  
Orlando Chaparro ◽  
Jaison Daniel Cucarián
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Physical Exercise ◽  
Disease Progression ◽  
Neuronal Damage ◽  
Experimental Studies ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Effects ◽  
Local Inflammatory Response ◽  
Neuroinflammatory Response

Multiple sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by central nervous system (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Mesenchymal stem cells as a treatment for multiple sclerosis: a focus on experimental animal studies

2020 ◽  
Vol 31 (2) ◽  
pp. 161-179 ◽  
Author(s):  
Ahmed Lotfy ◽  
Nourhan S. Ali ◽  
Mai Abdelgawad ◽  
Mohamed Salama
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Animal Studies ◽  
Culture Medium ◽  
Therapeutic Effects ◽  
Autoimmune Encephalomyelitis ◽  
Main Factors ◽  
Experimental Autoimmune

AbstractMultiple sclerosis (MS) is a progressive and debilitating neurological condition in which the immune system abnormally attacks the myelin sheath insulating the nerves. Mesenchymal stem cells (MSCs) are found in most adult tissues and play a significant systemic role in self-repair. MSCs have promising therapeutic effects in many diseases, such as autoimmune diseases, including MS. MSCs have been tested in MS animal models, such as experimental autoimmune encephalomyelitis. Other studies have combined other agents with MSCs, genetically modified MSCs, or used culture medium from MSCs. In this review, we will summarize these studies and compare the main factors in each study, such as the source of MSCs, the type of animal model, the route of injection, the number of injected cells, and the mechanism of action.

scholarly journals Mesenchymal stem cell applications in polycystic ovary syndrome treatment

2021 ◽  
Vol 38 (3) ◽  
pp. 361-366
Author(s):  
Mehmet Volkan BULBUL ◽  
Berna YILDIRIM ◽  
Bircan KOLBASI ◽  
İlknur KESKIN
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Polycystic Ovary Syndrome ◽  
Spinal Cord Injuries ◽  
Polycystic Ovary ◽  
Experimental Studies ◽  
Tooth Pulp ◽  
Therapeutic Effects ◽  
Ovary Syndrome ◽  
Paracrine Factors

Mesenchymal stem cells (MSCs) are highly capable of self-renewal and differentiation. They can be isolated from a variety of sources such as adipose tissue, bone marrow, umbilical cord, tooth pulp and can be cultured under in vitro conditions. MSCs have anti-inflammatory, anti-apoptotic, angiogenic, immunomodulatory and many more therapeutic effects due to the effects of paracrine factors they secrete. Today, mesenchymal stem cells are used for treatment in more than twenty diseases, from spinal cord injuries to diabetes. However, there is little mention in the literature of the use of these cells in female reproductive system diseases. In this review, a limited number of clinical and experimental studies on the use of mesenchymal stem cells in the treatment of polycystic ovary syndrome, which is very common in women, were examined and analyzed.

scholarly journals Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Lina Samira Bahr ◽  
Markus Bock ◽  
Daniela Liebscher ◽  
Judith Bellmann-Strobl ◽  
Liane Franz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Clinical Evidence ◽  
Controlled Study ◽  
Intermittent Fasting ◽  
Therapeutic Effects ◽  
Randomized Controlled ◽  
Markers Of Inflammation ◽  
Ketogenic Diets

Abstract Background Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing–remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20–40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS. Trial registration ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.

scholarly journals Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-30 ◽  
Author(s):  
Ankit Tandon ◽  
Sangh Jyoti Singh ◽  
Rajnish Kumar Chaturvedi
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Behavioral Deficits ◽  
Cell Therapies ◽  
Proliferation And Differentiation

Alzheimer’s disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.

scholarly journals Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

2019 ◽  
Author(s):  
Lina Samira Bahr ◽  
Markus Bock ◽  
Daniela Liebscher ◽  
Judith Bellmann-Strobl ◽  
Liane Franz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Study ◽  
Disease Progression ◽  
Clinical Evidence ◽  
Controlled Study ◽  
Intermittent Fasting ◽  
Therapeutic Effects ◽  
Dietary Interventions ◽  
Randomized Controlled ◽  
Markers Of Inflammation

Abstract Background: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate if a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions. The dietary interventions are 1) a KD with a restricted carbohydrate intake of 20-40 g/day, 2) a FD with a 7 day fast every 6 months and 14 hours daily intermittent fasting in between, and 3) a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion: Preclinical data suggest that KD and FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and FD on disease progression of MS. Trial Registration: ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414

scholarly journals Unraveling the therapeutic effects of mesenchymal stem cells in asthma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Mirershadi ◽  
Mahdi Ahmadi ◽  
Aysa Rezabakhsh ◽  
Hadi Rajabi ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Current Knowledge ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Effects ◽  
Pulmonary Tissue ◽  
Chronic Inflammatory Response ◽  
Asthmatic Patients ◽  
Cell Based Therapy ◽  
Cell Sources

Abstract Asthma is a chronic inflammatory disease associated with airway hyper-responsiveness, chronic inflammatory response, and excessive structural remodeling. The current therapeutic strategies in asthmatic patients are based on controlling the activity of type 2 T helper lymphocytes in the pulmonary tissue. However, most of the available therapies are symptomatic and expensive and with diverse side outcomes in which the interruption of these modalities contributes to the relapse of asthmatic symptoms. Up to date, different reports highlighted the advantages and beneficial outcomes regarding the transplantation of different stem cell sources, and relevant products from for the diseases’ alleviation and restoration of injured sites. However, efforts to better understand by which these cells elicit therapeutic effects are already underway. The precise understanding of these mechanisms will help us to translate stem cells into the clinical setting. In this review article, we described current knowledge and future perspectives related to the therapeutic application of stem cell-based therapy in animal models of asthma, with emphasis on the underlying therapeutic mechanisms.

scholarly journals Gene Therapy of Multiple Sclerosis Using Interferonβ-Secreting Human Bone Marrow Mesenchymal Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chung Heon Ryu ◽  
Kwang Ywel Park ◽  
Yun Hou ◽  
Chang Hyun Jeong ◽  
Seong Muk Kim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Average Score ◽  
Lumbar Spinal Cord ◽  
Therapeutic Effects ◽  
Inflammatory Infiltration

Interferon-beta (IFN-β), a well-established standard treatment for multiple sclerosis (MS), has proved to exhibit clinical efficacy. In this study, we first evaluated the therapeutic effects for MS using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) as delivery vehicles with lesion-targeting capability and IFN-βas therapeutic gene. We also engineered hBM-MSCs to secret IFN-β(MSCs-IFNβ) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFNβby an ELISA assay. MSCs-IFNβ-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and the maximum and average score for all animals in each group was significantly lower in the MSCs-IFNβ-treated EAE mice when compared with the MSCs-GFP-treated EAE mice. Inflammatory infiltration and demyelination in the lumbar spinal cord also significantly decreased in the MSCs-IFNβ-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFNβtreatment enhanced the immunomodulatory effects, which suppressed proinflammatory cytokines (IFN- and TNF-) and conversely increased anti-inflammatory cytokines (IL-4 and IL-10). Importantly, injected MSCs-IFNβmigrated into inflamed CNS and significantly reduced further injury of blood-brain barrier (BBB) permeability in EAE mice. Thus, our results provide the rationale for designing novel experimental protocols to enhance the therapeutic effects for MS using hBM-MSCs as an effective gene vehicle to deliver the therapeutic cytokines.

scholarly journals Interferon-beta changes the expression of IL10, IL23A and FOXP3 on Multiple Sclerosis patients' T cells

2021 ◽  
Author(s):  
Hazal Gezmis ◽  
Tansu Doran ◽  
Saime Fusun Mayda Domac ◽  
Deniz Yucel ◽  
Rahsan Karaci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Disease Progression ◽  
Drug Concentration ◽  
Interferon Beta ◽  
Mononuclear Cells ◽  
Therapeutic Effects ◽  
Gene Expressions ◽  
Peripheral Blood Mononuclear ◽  
Multiple Sclerosis Patients

Aim of the Study: Multiple sclerosis (MS) is an autoimmune disorder causing demyelination in axons. Available therapies target different molecules, but not all have therapeutic effects on disease progression, and this effect can only be seen after a long-time administration. Interferon beta (IFN-β), an MS therapy for many years, slows down the disease progression and reduces disease symptoms by targeting T cells. Yet, a considerable portion of the patient has experienced no therapeutic response to IFN-β. It is necessary to determine disease-specific biomarkers which allow early diagnosis or treatment of MS. Here, it was aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A) as well as forkhead box P3 (FOXP3) genes on MS after IFN-β therapy. Materials & Methods: Peripheral blood mononuclear cells (PBMCs) were extracted to isolate CD4+ and CD25+ T cells. Cytotoxicity assays were performed on each cell type for determining optimum drug concentration. Then, cells were cultured and determined drug concentration was administered to the cells to measure gene expressions with RT-PCR. Results: It was found that the cytotoxic effect of IFN-β was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-β. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48h in CD4+ T cells. For CD25+ T cells, the graded increase of FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake, significantly. Conclusion: Although considerable change in expression was obtained, the long-term IFN-β effect on both genes and cells should be determined by follow-up at least a year. Keywords: MS, IFN-β, IL23A, FOXP3, IL10, T cells

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