scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Mechanisms of Action of Human Mesenchymal Stem Cells in Tissue Repair Regeneration and their Implications

2017 ◽  
Vol 53 (02) ◽  
pp. 104-120 ◽  
Author(s):  
Manisha Singh ◽  
Suchi Gupta ◽  
Sonali Rawat ◽  
Swati Midha ◽  
Krishan Gopal Jain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Human Mesenchymal Stem Cells ◽  
Mechanisms Of Action ◽  
Maximum Output ◽  
Cell Replacement Therapy ◽  
Tissue Repair And Regeneration

ABSTRACTCell replacement therapy holds a promising future in the treatment of degenerative diseases related to neuronal, cardiac and bone tissues. In such kind of diseases, there is a progressive loss of specific types of cells. Currently the most upcoming and trusted cell candidate is Mesenchymal Stem Cells (MSCs) as these cells are easy to isolate from the tissue, easy to maintain and expand and no ethical concerns are linked. MSCs can be obtained from a number of sources like bone marrow, umbilical cord blood, umbilical cord, dental pulp, adipose tissues, etc. MSCs help in tissue repair and regeneration by various mechanisms of action like cell differentiation, immunomodulation, paracrine effect, etc. The future of regenerative medicine lies in tissue engineering and exploiting various properties to yield maximum output. In the current review article, we have targeted the repair and regeneration mechanisms of MSCs in neurodegenerative diseases, cardiac diseases and those related to bones. Yet there is a lot to understand, discover and then understand again about the molecular mechanisms of MSCs and then applying this knowledge in developing the therapy to get maximum repair and regeneration of concerned tissue and in turn the recovery of the patient.

scholarly journals Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Treatment of Viral Diseases

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 409
Author(s):  
Carl Randall Harrell ◽  
Biljana Popovska Jovicic ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Trophic Factors ◽  
Viral Diseases ◽  
Antiviral Immune Response ◽  
Tissue Repair And Regeneration ◽  
Infected Cells ◽  
Almost All

Mesenchymal stem cells (MSCs) are adult, immunomodulatory stem cells which reside in almost all postnatal tissues. Viral antigens and damage-associated molecular patterns released from injured and infected cells activate MSCs, which elicit strong antiviral immune response. MSC-sourced interferons and inflammatory cytokines modulate the cytotoxicity of NK cells and CTLs, enhance the antigen-presentation properties of DCs and macrophages, regulate cytokine synthesis in CD4+ T helper cells and promote antibody production in B cells. After the elimination of viral pathogens, MSCs produce immunoregulatory cytokines and trophic factors, prevent the over-activation of immune cells and promote tissue repair and regeneration. In this review article, we summarize the current knowledge on the molecular mechanisms that are responsible for the MSC-dependent elimination of virus-infected cells, and we emphasize the therapeutic potential of MSCs and their secretomes in the treatment of viral diseases.

scholarly journals The Role of Mesenchymal Stem Cells in Radiation-Induced Lung Fibrosis

2019 ◽  
Vol 20 (16) ◽  
pp. 3876 ◽  
Author(s):  
Zanoni ◽  
Cortesi ◽  
Zamagni ◽  
Tesei
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Fibrosis ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Acute Stage ◽  
Lung Epithelial Cells ◽  
Treatment Modalities ◽  
Tissue Repair And Regeneration ◽  
Radiation Induced

Radiation therapy is one of the most important treatment modalities for thoracic tumors. Despite significant advances in radiation techniques, radiation-induced lung injury (RILI) still occurs in up to 30% of patients undergoing thoracic radiotherapy, and therefore remains the main dose-limiting obstacle. RILI is a potentially lethal clinical complication of radiotherapy that has 2 main stages: an acute stage defined as radiation pneumonitis, and a late stage defined as radiation-induced lung fibrosis. Patients who develop lung fibrosis have a reduced quality of life with progressive and irreversible organ malfunction. Currently, the most effective intervention for the treatment of lung fibrosis is lung transplantation, but the lack of available lungs and transplantation-related complications severely limits the success of this procedure. Over the last few decades, advances have been reported in the use of mesenchymal stem cells (MSCs) for lung tissue repair and regeneration. MSCs not only replace damaged lung epithelial cells but also promote tissue repair through the secretion of anti-inflammatory and anti-fibrotic factors. Here, we present an overview of MSC-based therapy for radiation-induced lung fibrosis, focusing in particular on the molecular mechanisms involved and describing the most recent preclinical and clinical studies carried out in the field.

scholarly journals Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity

2021 ◽  
Vol 22 (22) ◽  
pp. 12429
Author(s):  
Carl Randall Harrell ◽  
Ana Volarevic ◽  
Valentin G. Djonov ◽  
Nemanja Jovicic ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Cellular Mechanisms ◽  
Multipotent Stem Cells ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.

scholarly journals Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jennifer Steens ◽  
Diana Klein
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Human Mesenchymal Stem Cells ◽  
Human Mscs ◽  
Multipotent Stem Cells ◽  
Adult Organism ◽  
Almost All

Mesenchymal stem cells (MSCs) are heterogeneous multipotent stem cells that are involved in the development of mesenchyme-derived evolving structures and organs during ontogeny. In the adult organism, reservoirs of MSCs can be found in almost all tissues where MSCs contribute to the maintenance of organ integrity. The use of these different MSCs for cell-based therapies has been extensively studied over the past years, which highlights the use of MSCs as a promising option for the treatment of various diseases including autoimmune and cardiovascular disorders. However, the proportion of MSCs contained in primary isolates of adult tissue biopsies is rather low and, thus, vigorous ex vivo expansion is needed especially for therapies that may require extensive and repetitive cell substitution. Therefore, more easily and accessible sources of MSCs are needed. This review summarizes the current knowledge of the different strategies to generate human MSCs in vitro as an alternative method for their applications in regenerative therapy.

scholarly journals Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lite Ge ◽  
Chengfeng Xun ◽  
Wenshui Li ◽  
Shengyu Jin ◽  
Zuo Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Olfactory Mucosa ◽  
Luciferase Reporter ◽  
Treatment Benefit ◽  
Tissue Repair And Regeneration

AbstractMesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, the molecular mechanisms underlying hypoxic MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators of cell-to-cell communication and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of EVs from human hypoxic olfactory mucosa MSCs (OM-MSCs) on angiogenesis and its underlying mechanism. EVs were isolated from normoxic (N) OM-MSCs (N-EVs) and hypoxic (H) OM-MSCs (H-EVs) using differential centrifugation and identified by transmission electron microscopy and flow cytometry. In vitro and in vivo, both types of OM-MSC-EVs promoted the proliferation, migration, and angiogenic activities of human brain microvascular endothelial cells (HBMECs). In addition, angiogenesis-stimulatory activity in the H-EV group was significantly enhanced compared to the N-EV group. MicroRNA profiling revealed a higher abundance of miR-612 in H-EVs than in N-EVs, while miR-612 inactivation abolished the N-EV treatment benefit. To explore the roles of miR-612, overexpression and knock-down experiments were performed using a mimic and inhibitor or agomir and antagomir of miR-612. The miR-612 target genes were confirmed using the luciferase reporter assay. Gain- and loss-of-function studies allowed the validation of miR-612 (enriched in hypoxic OM-MSC-EVs) as a functional messenger that stimulates angiogenesis and represses the expression of TP53 by targeting its 3′-untranslated region. Further functional assays showed that hypoxic OM-MSC-EVs promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular endothelial growth factor (VEGF) signaling in HBMECs via the exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest that hypoxic OM-MSC-EVs may represent a promising strategy for ischemic disease by promoting angiogenesis via miR-612 transfer. Graphical Abstract

scholarly journals Long non-coding RNA HULC affects the proliferation, apoptosis, migration, and invasion of mesenchymal stem cells

2018 ◽  
Vol 243 (13) ◽  
pp. 1074-1082 ◽  
Author(s):  
Xiujun Li ◽  
Jiali Wang ◽  
Yuchen Pan ◽  
Yujun Xu ◽  
Dan Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cancer ◽  
Clinical Application ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Non Coding Rna ◽  
And Function ◽  
Long Non Coding Rna

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.

scholarly journals Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair

2020 ◽  
Vol 21 (5) ◽  
pp. 1638 ◽  
Author(s):  
Emilia Di Giovanni ◽  
Silvia Buonvino ◽  
Ivano Amelio ◽  
Sonia Melino
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Tissue Repair ◽  
Dermal Fibroblasts ◽  
Water Soluble ◽  
Dependent Manner ◽  
Tissue Repair And Regeneration ◽  
Stem Cell Delivery ◽  
Cell Based Therapy

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

scholarly journals Mesenchymal stem cells’ homing and cardiac tissue repair

2019 ◽  
Author(s):  
Renata Szydlak
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Repair ◽  
Cardiac Tissue ◽  
Cellular Therapy ◽  
Current Knowledge ◽  
Target Tissue ◽  
Intramyocardial Injection ◽  
Inflammatory Conditions ◽  
Cardiac Disorders

Nowadays, mesenchymal stem cells (MSCs) are essential players in cellular therapy and regenerative medicine. MSCs are used to treat cardiac disorders by intramyocardial injection or injection into the bloodstream. Therefore, a premise of successful MSC-based therapy is that the cells reach the site of injury and home the damaged tissue. In response to inflammatory conditions, MSCs can potentially move into the place of injury and colonize damaged tissues, where they participate in their regeneration. This review presents the current knowledge of the mechanisms of MSCs migration and target tissue homing in the field of cardiovascular therapies.

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