scholarly journals Extracellular vesicles for tissue repair and regeneration: evidence, challenges and opportunities

2021 ◽  
Author(s):  
Anika Nagelkerke ◽  
Miina Ojansivu ◽  
Luke van der Koog ◽  
Thomas E. Whittaker ◽  
Eoghan M. Cunnane ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Tissue Repair And Regeneration ◽  
Challenges And Opportunities

scholarly journals An apoptosis-driven ‘onco-regenerative niche’: roles of tumour-associated macrophages and extracellular vesicles

2017 ◽  
Vol 373 (1737) ◽  
pp. 20170003 ◽  
Author(s):  
Christopher D. Gregory ◽  
Margaret Paterson
Keyword(s):  
Extracellular Vesicles ◽  
Tumour Cell ◽  
Cell Apoptosis ◽  
Tissue Repair ◽  
B Cell Lymphoma ◽  
Cell Loss ◽  
Endothelial Activation ◽  
Tumour Microenvironment ◽  
Malignant Tumours ◽  
Tissue Repair And Regeneration

The cell-death programme, apoptosis, is well established as a tumour suppressor mechanism. Paradoxically, high levels of apoptosis in tumours are closely coupled with poor prognosis. Indeed, where it has been studied, cell loss is a striking feature of high-grade cancers, illustrating the importance of considering malignant disease as an imbalance between cell gain and cell loss that favours cell gain rather than as a unidirectional disorder of cell gain alone. In addition to orchestrating cell loss, apoptosis can signal regenerative responses—for example compensatory proliferation—in neighbouring cells. Accumulating evidence suggests that normal tissue repair and regenerative processes are hijacked in the malignant tissue microenvironment such that cancer may be likened to a ‘wound that fails to stop repairing’. We have proposed that a critical requirement for the successful growth, progression and re-growth of malignant tumours is a complex milieu, conceptually termed the ‘onco-regenerative niche’, which is composed, in addition to transformed neoplastic cells, of a network of normal cells and factors activated as if in tissue repair and regeneration. Our work is based around the hypothesis that tumour cell apoptosis, macrophage activation and endothelial activation are key, interlinked elements of the onco-regenerative niche and that apoptotic tumour cell–derived extracellular vesicles provide critical intercellular communication vehicles of the niche. In aggressive B-cell lymphoma, tumour cell apoptosis promotes both angiogenesis and the accumulation of pro-tumour macrophages in the lymphoma microenvironment. Furthermore, apoptotic lymphoma-derived extracellular vesicles have potent pro-tumour potential. These findings have important implications for the roles of apoptosis in regulation of malignant diseases and for the efficacy of apoptosis-inducing anti-cancer therapies. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Regulating the production and biological function of small extracellular vesicles: current strategies, applications and prospects

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei Luo ◽  
Zhi Wu ◽  
Yang Wang ◽  
Haiyan Li
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Biological Function ◽  
Cell Aging ◽  
Bioactive Substances ◽  
Practical Applications ◽  
Production Capability ◽  
Tissue Repair And Regeneration ◽  
Donor Cells ◽  
Cellular Behaviors

AbstractNumerous studies have confirmed the great application potentials of small extracellular vesicles (sEVs) in biological medical field, especially in tissue repair and regeneration. However, the production capability of sEVs by noncancerous cells is very limited, while their dosage requirements in disease treatments are usually very high. Meanwhile, as cell aging, the sEV production capability of cells decreases and the biological function of sEVs changes accordingly. In addition, for special applications, sEVs carrying desired bioactive substances should be designed to perform their expected biological function. Therefore, improving the production of sEVs and precisely regulating their biological function are of great significance for promoting the clinical applications of sEVs. In this review, some of the current classic strategies in affecting the cellular behaviors of donor cells and subsequently regulating the production and biological function of their sEVs are summarized, including gene engineering methods, stress-inducing conditions, chemical regulators, physical methods, and biomaterial stimulations. Through applying these strategies, increased yield of sEVs with required biological function can be obtained for disease treatment and tissue repair, such as bone regeneration, wound healing, nerve function recovery and cancer treatment, which could not only reduce the harvest cost of sEV but promote the practical applications of sEVs in clinic. Graphical Abstract

Circulating extracellular vesicles: Their role in tissue repair and regeneration

2016 ◽  
Vol 55 (1) ◽  
pp. 53-61 ◽  
Author(s):  
José H. Teixeira ◽  
Andreia M. Silva ◽  
Maria Ines Almeida ◽  
Mário A. Barbosa ◽  
Susana G. Santos
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Tissue Repair And Regeneration

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 Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis

2021 ◽  
Vol 22 (15) ◽  
pp. 7960
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Jing-Long Huang ◽  
Jenn-Haung Lai
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Macrophage Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Inflammatory Joint Diseases ◽  
Tissue Repair And Regeneration ◽  
Related Cell ◽  
Key Players

Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and regeneration. Juvenile idiopathic arthritis (JIA) is an umbrella term describing inflammatory joint diseases in children. Accumulated evidence suggests a link between Mo and Mφ activation and JIA pathogenesis. Accordingly, topics regarding the signals and mechanisms regulating Mo and Mφ activation leading to pathologies in patients with JIA are of great interest. In this review, we critically summarize recent advances in the understanding of how Mo and Mφ activation is involved in JIA pathogenesis and focus on the signaling pathways and mechanisms participating in the related cell activation processes.

scholarly journals Repair cell first, then regenerate the tissues and organs

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao-Bing Fu
Keyword(s):  
Tissue Repair ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Severe Trauma ◽  
Basic Unit ◽  
Basic Process ◽  
Tissue Repair And Regeneration ◽  
Healing Tissue ◽  
Organ Repair ◽  
And Function

AbstractWound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly; however, the basic process of repair at the cell level is often neglected. Because the cell is the basic unit of organism structure and function; cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury. Then, damage to tissues and organs occurs with massive cell damage, apoptosis and even cell death. Thus, how to achieve the aim of perfect repair and regeneration? The basic process of tissue or organ repair and regeneration should involve repair of cells first, then tissues and organs. In this manuscript, it is my consideration about how to repair the cell first, then regenerate the tissues and organs.

scholarly journals Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro

2021 ◽  
Vol 22 (2) ◽  
pp. 958
Author(s):  
Luca Tamò ◽  
Kleanthis Fytianos ◽  
Fabienne Caldana ◽  
Cedric Simillion ◽  
Anis Feki ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Critical Role ◽  
Organ Injury ◽  
Macrophage Phenotype ◽  
Gene Interaction Network ◽  
Tissue Repair And Regeneration ◽  
Secretory Pattern

Induced pluripotent stem cell secretome (iPSC-CM) mitigate organ injury and help in repair. Macrophages play a critical role in tissue repair and regeneration and can be directed to promote tissue repair by iPSC-CM, although the exact mechanisms are not known. In the current investigative study, we evaluated the possible mechanism by which iPSC-CM regulates the phenotype and secretory pattern of macrophages in vitro. Macrophages were obtained from human peripheral blood mononuclear cells and differentiated to various subpopulations and treated with either iPSC-CM or control media in vitro. Macrophage phenotype was assessed by flow cytometry, gene expression changes by qRT PCR and secretory pattern by multiplex protein analysis. The protein and gene interaction network revealed the involvement of Amyloid precursor protein (APP) and ELAV-like protein 1 (ELAVL-1) both present in the iPSC-CM to play an important role in regulating the macrophage phenotype and their secretory pattern. This exploratory study reveals, in part, the possible mechanism and identifies two potential targets by which iPSC-CM regulate macrophages and help in repair and regeneration.

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.

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