scholarly journals Vitamin D3 and Dental Mesenchymal Stromal Cells

2020 ◽  
Vol 10 (13) ◽  
pp. 4527
Author(s):  
Oleh Andrukhov ◽  
Alice Blufstein ◽  
Christian Behm ◽  
Andreas Moritz ◽  
Xiaohui Rausch-Fan
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Vitamin D3 ◽  
Stromal Cells ◽  
Biologically Active ◽  
Dental Tissue ◽  
Therapeutic Modalities ◽  
Dental Tissues ◽  
Physiological Processes ◽  
Vitamin D3 Metabolites ◽  
Almost All

Vitamin D3 is a hormone involved in the regulation of bone metabolism, mineral homeostasis, and immune response. Almost all dental tissues contain resident mesenchymal stromal cells (MSCs), which are largely similar to bone marrow-derived MSCs. In this narrative review, we summarized the current findings concerning the physiological effects of vitamin D3 on dental MSCs. The existing literature suggests that dental MSCs possess the ability to convert vitamin D3 into 25(OH)D3 and subsequently to the biologically active 1,25(OH)2D3. The vitamin D3 metabolites 25(OH)D3 and 1,25(OH)2D3 stimulate osteogenic differentiation and diminish the inflammatory response of dental MSCs. In addition, 1,25(OH)2D3 influences the immunomodulatory properties of MSCs in different dental tissues. Thus, dental MSCs are both producers and targets of 1,25(OH)2D3 and might regulate the local vitamin D3-dependent processes in an autocrine/paracrine manner. The local vitamin D3 metabolism is assumed to play an essential role in the local physiological processes, but the mechanisms of its regulation in dental MSCs are mostly unknown. The alteration of the local vitamin D3 metabolism may unravel novel therapeutic modalities for the treatment of periodontitis as well as new strategies for dental tissue regeneration.

scholarly journals Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Guoping Zheng ◽  
Menghua Ge ◽  
Guanguan Qiu ◽  
Qiang Shu ◽  
Jianguo Xu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spinal Cord Injuries ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cell Contact ◽  
Direct Cell ◽  
Almost All ◽  
Preclinical And Clinical Studies ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.

scholarly journals Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Sandonà ◽  
Lorena Di Pietro ◽  
Federica Esposito ◽  
Alessia Ventura ◽  
Antonietta Rosa Silini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Muscle Regeneration ◽  
Point Of View ◽  
Biologically Active ◽  
Therapeutic Interventions ◽  
Skeletal Muscle Regeneration ◽  
Therapeutic Effects ◽  
Muscular Diseases

Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.

scholarly journals Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview

2021 ◽  
Vol 2 ◽  
Author(s):  
Alessia Paganelli ◽  
Oriana Trubiani ◽  
Francesca Diomede ◽  
Alessandra Pisciotta ◽  
Roberto Paganelli
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Inflammatory Mediators ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Alveolar Bone ◽  
Deciduous Teeth ◽  
Cell Reactivity ◽  
Dental Tissues ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and specific surface markers (CD105, CD73, CD90, STRO-1, CD106, and CD146), common to all other MSC subtypes. Dental pulp, periodontal ligament, apical papilla, human exfoliated deciduous teeth, alveolar bone, dental follicle, tooth germ, and gingiva are all different sources for isolation and expansion of MSCs. Dental MSCs have regenerative and immunomodulatory properties; they are scarcely immunogenic but actively modulate T cell reactivity. in vitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on peripheral blood mononuclear cell proliferation, clearance of apoptotic cells, and promotion of a shift in the Treg/Th17 cell ratio. Appropriately stimulated MSCs produce anti-inflammatory mediators, such as transforming growth factor-β (TGF-β), prostaglandin E2, and interleukin (IL)-10. A particular mechanism through which MSCs exert their immunomodulatory action is via the production of extracellular vesicles containing such anti-inflammatory mediators. Recent studies demonstrated MSC-mediated inhibitory effects both on monocytes and activated macrophages, promoting their polarization to an anti-inflammatory M2-phenotype. A growing number of trials focusing on MSCs to treat autoimmune and inflammatory conditions are ongoing, but very few use dental tissue as a cellular source. Recent results suggest that dental MSCs are a promising therapeutic tool for immune-mediated disorders. However, the exact mechanisms responsible for dental MSC-mediated immunosuppression remain to be clarified, and impairment of dental MSCs immunosuppressive function in inflammatory conditions and aging must be assessed before considering autologous MSCs or their secreted vesicles for therapeutic purposes.

scholarly journals Course correction of adjuvant arthritis with cryopreserved multipotent mesenchymal stromal cells

2021 ◽  
Vol 12 (3) ◽  
pp. 545-553
Author(s):  
D. B. Vvedenskyi ◽  
N. O. Volkova ◽  
M. S. Yukhta ◽  
N. O. Ashukina ◽  
A. M. Goltsev
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adjuvant Arthritis ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cyclooxygenase 2 ◽  
Biologically Active ◽  
Cartilage Tissue ◽  
Control Group ◽  
Regenerative Processes ◽  
And Cartilage

Rheumatoid arthritis is an inflammatory autoimmune disease that occurs as a result of impaired immune tolerance, leading to an aberrant immune response to autologous antigens. Multipotent mesenchymal stromal cells (MMSCs) and the biologically active substances they produce can promote the activation of regenerative processes in the organism not only by direct cell differentiation, but also due to their inherent trophic and immunosuppressive potentials. The aim of the study was to experimentally evaluate changes in the course of the acute phase of adjuvant arthritis upon local and generalized administration of cryopreserved MMSCs from adipose and cartilage tissues. The results of histological, imunohistochemical and biochemical studies showed that the animals of the control group throughout the observation period developed an inflammatory process, which manifested in joint swelling (increased arthritis index), leukocytosis, spread of chondrocyte-free zones, weakening of staining, loss of clarity of cartilage tissue contours, increased content of cyclooxygenase-2, reduced glycosaminoglycan content and total antioxidant defense system activity. At the same time, the local administration of cryopreserved MMSCs from adipose and cartilage tissues contributed to the normalization of the structural and functional organization, content of glycosaminoglycans and cyclooxygenase-2 with complete recovery of blood parameters. Less pronounced regeneration processes in articular cartilage occurred under generalized administration of cryopreserved MMSCs from adipose and cartilage tissues in comparison with the local method. However, the difference between the control and experimental groups indicates the ability of cryopreserved MMSCs to influence the intensity of regenerative processes in damaged cartilage tissue with both methods of administration. Comparative evaluation of the use of cryopreserved MMSCs from adipose and cartilage tissues showed the absence of significant changes in the studied indicators. These data can be used to substantiate and develop methods of arthritis treatment in clinical practice.

scholarly journals The Effects of Hypoxia on the Immune-Modulatory Properties of Bone Marrow-Derived Mesenchymal Stromal Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zsolt Fábián
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Current Knowledge ◽  
Developed Countries ◽  
Oxygen Depletion ◽  
Therapeutic Modalities ◽  
The Impact

The therapeutic repertoire for life-threatening inflammatory conditions like sepsis, graft-versus-host reactions, or colitis is very limited in current clinical practice and, together with chronic ones, like the osteoarthritis, presents growing economic burden in developed countries. This urges the development of more efficient therapeutic modalities like the mesenchymal stem cell-based approaches. Despite the encouraging in vivo data, however, clinical trials delivered ambiguous results. Since one of the typical features of inflamed tissues is decreased oxygenation, the success of cellular therapy in inflammatory pathologies seems to be affected by the impact of oxygen depletion on transplanted cells. Here, we examine our current knowledge on the effect of hypoxia on the physiology of bone marrow-derived mesenchymal stromal cells, one of the most popular tools of practical cellular therapy, in the context of their immune-modulatory capacity.

Mesenchymal Stromal Cells (MSCs): a promising tool for cell-based angiogenic therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Cristiana Ulpiano ◽  
Cláudia L. da Silva ◽  
Gabriel A. Monteiro
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Genetic Material ◽  
Biologically Active ◽  
Human Mscs ◽  
Comprehensive Overview ◽  
Cell Functions ◽  
Cell Based Therapy ◽  
Wide Range

: The Mesenchymal stromal cells (MSCs) are a diverse subset of adult multipotent precursors, known for their potential therapeutic properties in regenerative medicine mainly sustained by paracrine effects, through secretion of a variety of biologically active molecules. MSC secretome includes a wide range of soluble protein factors, composed of growth factors and cytokines, and vesicular components, which transfer proteins and genetic material modulating the host microenvironment. In particular, MSC-derived secretome mediates the different steps of the angiogenic process, inducing endothelial cell functions in vitro and promoting angiogenesis in vivo. As a result, MSCs have been widely explored as a promising cell-based therapy in diseases caused by insufficient angiogenesis. Numerous studies of myocardial infarction, ischemic stroke and critical limb ischemia in animals have shown that human MSCs can enhance angiogenesis and accelerate tissue regeneration. This extensive preclinical work encouraged the study of these remarkable cells for the treatment of these disorders in human clinical settings. The present review provides a comprehensive overview of the pro-angiogenic potential of MSCs and paracrine effectors of their secretome. In addition, bioengineering strategies including ex vivo preconditioning and genetic modification approaches, to enhance MSC innate angiogenic properties, and thereby therapeutic potency, will be presented. Finally, an update on completed preclinical and clinical studies with MSCs for the treatment of ischemia-related diseases will be discussed.

scholarly journals Hopes and Hurdles of Employing Mesenchymal Stromal Cells in the Treatment of Cardiac Fibrosis

2021 ◽  
Vol 22 (23) ◽  
pp. 13000
Author(s):  
Sebastian Neuber ◽  
Maximilian Y. Emmert ◽  
Timo Z. Nazari-Shafti
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Matrix Proteins ◽  
Stress Injury ◽  
High Prevalence ◽  
Improve Heart Function ◽  
Response To Stress ◽  
Almost All

Excessive cardiac fibrosis plays a crucial role in almost all types of heart disease. Generally, cardiac fibrosis is a scarring process triggered in response to stress, injury, or aging and is characterized by the accumulation of activated myofibroblasts that deposit high levels of extracellular matrix proteins in the myocardium. While it is beneficial for cardiac repair in the short term, it can also result in pathological remodeling, tissue stiffening, and cardiac dysfunction, contributing to the progression of heart failure, arrhythmia, and sudden cardiac death. Despite its high prevalence, there is a lack of effective and safe therapies that specifically target myofibroblasts to inhibit or even reverse pathological cardiac fibrosis. In the past few decades, cell therapy has been under continuous evaluation as a potential treatment strategy, and several studies have shown that transplantation of mesenchymal stromal cells (MSCs) can reduce cardiac fibrosis and improve heart function. Mechanistically, it is believed that the heart benefits from MSC therapy by stimulating innate anti-fibrotic and regenerative reactions. The mechanisms of action include paracrine signaling and cell-to-cell interactions. In this review, we provide an overview of the anti-fibrotic properties of MSCs and approaches to enhance them and discuss future directions of MSCs for the treatment of cardiac fibrosis.

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