scholarly journals Human bone marrow mesenchymal stem/stromal cell behaviour is coordinated via mechanically activated osteocyte-derived extracellular vesicles

2019 ◽  
Author(s):  
Kian F. Eichholz ◽  
Ian Woods ◽  
Gillian P. Johnson ◽  
Nian Shen ◽  
Michele Corrigan ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Stromal Cell ◽  
Osteogenic Potential ◽  
Human Mscs ◽  
Fluid Shear ◽  
Paracrine Factors ◽  
Cell Behaviour ◽  
Mechanical Conditioning ◽  
Effector Cells ◽  
A Cell

AbstractOsteocytes are mechanosensitive cells that are believed to play a fundamental role in coordinating bone mechanoadaptation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to effector cells is poorly understood. In this study, we demonstrated that osteocytes subjected to a physiologic fluid shear secrete a distinct collection of factors that significantly enhance human MSC recruitment and osteogenesis. Utilising proteomics we generated an extensive map of proteins within the mechanically activated osteocyte secretome, identifying numerous paracrine factors that are modified by mechanical stimulation. Moreover, we identified the presence of extracellular vesicles (EVs) and further demonstrated that these mechanically activated osteocyte derived EVs (MAEVs) coordinate human MSCs recruitment and osteogenesis. This indicates that mechanical conditioning of parent cells can modify EVs and demonstrates the pro-osteogenic potential of MAEVs as a cell-free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.

scholarly journals Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yoojin Seo ◽  
Hyung-Sik Kim ◽  
In-Sun Hong
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cells ◽  
Bilayer Membrane ◽  
Target Cells ◽  
Membrane Structures ◽  
Paracrine Factors ◽  
Immune Effector ◽  
Effector Cells ◽  
Conventional Cell ◽  
And Migration

Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.

scholarly journals Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in regenerative endodontics

2021 ◽  
Vol 41 ◽  
pp. 233-244
Author(s):  
A Ivica ◽  
◽  
M Zehnder ◽  
FE Weber
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Bioactive Molecules ◽  
In Vivo Studies ◽  
Human Mscs ◽  
Pulp Regeneration ◽  
Regenerative Endodontics ◽  
A Cell

Regenerative endodontic procedures are an alternative to conventional root-canal treatment and apexification. There are two different tissue engineering approaches that are currently followed, both aiming at the colonisation of the cleaned pulp space by pluripotent cells and subsequent pulp regeneration. Firstly, the transplantation of mesenchymal stem cells (MSCs), and secondly a cell-free strategy that relies on bioactive molecules to trigger the recruitment of the patient’s own cells. The first approach is hampered by costs and regulatory issues. Despite great initial enthusiasm with a clinically used cell-free approach that relies on induced bleeding into the pulp space, results have been revealed to be rather unpredictable, and mere repair rather than regeneration of the pulp-dentin complex is what is typically achieved. Moreover, the extent of further root development is variable, and the concept is limited to immature teeth. This article discusses a third possible way of regenerative endodontics that involves the application of MSC-derived exosomes. These are extracellular vesicles that contain proteins, lipids, and nucleic acids, reflecting the secretome of MSCs. Based on the first in vitro and in vivo studies, exosomes appear to be a potent tool to improve pulp regeneration. This narrative review aims to investigate the therapeutic use of human MSCs or dental pulp-derived exosomes in regenerative endodontics. Furthermore, the focus of this review is on targeting important questions that should be investigated in future in-vivo and clinical studies, such as the choice of scaffold material for exosome delivery into the pulp space.

scholarly journals A Good Manufacturing Practice–grade standard protocol for exclusively human mesenchymal stromal cell–derived extracellular vesicles

Cytotherapy ◽  
2017 ◽  
Vol 19 (4) ◽  
pp. 458-472 ◽  
Author(s):  
Karin Pachler ◽  
Thomas Lener ◽  
Doris Streif ◽  
Zsuzsanna A. Dunai ◽  
Alexandre Desgeorges ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Good Manufacturing Practice ◽  
Standard Protocol

Microglia extracellular vesicles: focus on molecular composition and biological function

2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Biological Effects ◽  
Genetic Material ◽  
Cell Communication ◽  
Molecular Composition ◽  
Cargo Proteins ◽  
A Cell ◽  
The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

scholarly journals Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells

2017 ◽  
Vol 47 (12) ◽  
pp. 2142-2152 ◽  
Author(s):  
Maria Pasztoi ◽  
Joern Pezoldt ◽  
Michael Beckstette ◽  
Christoph Lipps ◽  
Dagmar Wirth ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Regulatory T Cells ◽  
Extracellular Vesicles ◽  
Mesenteric Lymph Node ◽  
Stromal Cell ◽  
De Novo ◽  
Mesenteric Lymph
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