scholarly journals Composite Tissue Allotransplantation and Dysregulation in Tissue Repair and Regeneration: A Role for Mesenchymal Stem Cells

2013 ◽  
Vol 4 ◽  
Author(s):  
Anuja K. Antony ◽  
Katherine Rodby ◽  
Matthew K. Tobin ◽  
Megan I. O’Connor ◽  
Russell K. Pearl ◽  
...  
2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic

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.


2020 ◽  
Vol 21 (5) ◽  
pp. 1638 ◽  
Author(s):  
Emilia Di Giovanni ◽  
Silvia Buonvino ◽  
Ivano Amelio ◽  
Sonia Melino

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.


2017 ◽  
Vol 53 (02) ◽  
pp. 104-120 ◽  
Author(s):  
Manisha Singh ◽  
Suchi Gupta ◽  
Sonali Rawat ◽  
Swati Midha ◽  
Krishan Gopal Jain ◽  
...  

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.


2019 ◽  
Vol 20 (16) ◽  
pp. 3876 ◽  
Author(s):  
Zanoni ◽  
Cortesi ◽  
Zamagni ◽  
Tesei

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.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lite Ge ◽  
Chengfeng Xun ◽  
Wenshui Li ◽  
Shengyu Jin ◽  
Zuo Liu ◽  
...  

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


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