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How to cite this article: Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis.
Theranostics ; 8 5: Mesenchymal stem cells MSCs release extracellular vesicles EVs that display a therapeutic effect in inflammatory disease models. This prompted us to compare the function of exosomes Exos and microparticles MPs isolated from MSCs and investigate their immunomodulatory function in arthritis.
The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis.
MSCs are characterized by a multilineage differentiation potential and paracrine function through the release of multiple growth factors, chemokines and cytokines. One major role of MSCs is to suppress proliferation and function of cells of both innate and adaptive immunity [ 2 ]. Thanks to this property, they are widely investigated for their therapeutic properties in a variety of inflammatory and autoimmune diseases, including type 2 diabetes, experimental autoimmune encephalomyelitis or rheumatoid arthritis RA.
Among inflammatory models, the collagen-induced arthritis CIA murine model is of particular interest since it reproduces the main symptoms of RA both at clinical and biological levels [ 7 ].
It is a widely used model of arthritis, easily reproducible and useful for therapies evaluation. Another model of inflammation is delayed-type hypersensitivity DTH model, which is highly reproducible and induced in one week.
This is therefore a rapid, easy to manipulate and useful model for anti-inflammatory treatment evaluation [ 6 ]. In addition to being released in the extracellular milieu, a number of factors are proposed to be packaged into extracellular vesicles EVs and migrate throughout the body via the bloodstream.
EVs are small vesicles produced by virtually all cell types, characterized by a phospholipid bilayer and containing a large variety of proteins, mRNAs, and miRNAs [ 12 ]. Two main types of EVs are exosomes, or small vesicles diameter below nmproduced in the endosomal compartment in so-called multivesicular bodies, and microvesicles, or microparticles ranging from to nm in diameterreleased by budding of the plasma membrane.
In addition to size, the International Society of Extracellular Vesicles recently proposed minimal criteria to define EVs, including morphology, mechanism of cellular release and biochemical parameters [ 13 ]. Therapeutic efficacy of MSCs-derived EVs MSCs-EVs has been reported in different disease models, such as myocardial infarction and reperfusion injury, liver and kidney injury, hind limb ischemia and inflammatory diseases for review, see [ 14 ].
While much interest in MSCs-EVs for the treatment of many diseases has been shown, little is known on their exact function.
Moreover, no study has evaluated the role of MSCs-derived EVs in pre-clinical models relevant for rheumatoid arthritis [ 15 ].
In inflammatory conditions, an inhibitory function of MSCs-EVs on immune cell activation has been claimed in some studies while others reported absence of immunomodulatory effect [ 16 ]. Such discrepancies between studies might be due to differences in isolation protocols, but also to the activation state of MSCs during EVs production.
Moreover, the respective roles of different subtypes of EVs are poorly investigated. The second objective was to determine whether pre-activation of MSCs during preparation of conditioned media might impact the immunomodulatory effect of EVs.
Using an anti-viral functional assay, activity of the recombinant protein was measured to be 0. MSCs-CM distributed in 6 tubes containing CM was used pure in some experiments or further centrifuged for EVs isolation.
For Exos, supernatant from the MPs fraction was filtered through a 0. The pellet was washed and suspended in PBS. Visualization of EVs was assessed by transmission electron microscopy. EVs suspensions were loaded on Formvar-coated grids and negatively stained with uranyl acetate for 15 min.
For cell analysis, total splenocytes or isolated cell subsets were incubated in PBS containing 0. T lymphocyte proliferation assay and immune cell subset isolation and differentiation Murine splenocytes were isolated as described [ 10 ].
B cells were cultured in activation medium see above without beta-mercaptoethanol. B cells were activated with 2.California Christian Homeschool Family Torn Apart as Children are Medically Kidnapped, Forced into Public School, and Mother is Forced out of Family Home.
Stem cell laws are the law rules, and policy governance concerning the sources, research, and uses in treatment of stem cells in humans. These laws have been the source of much controversy and vary significantly by country. In the European Union, stem cell research using the human embryo is permitted in Sweden, Spain, Finland, Belgium, Greece, Britain, Denmark and the Netherlands; however, it.
It has long been known that light exerts powerful effects on the brain and on our well-being. Light is not only required for vision but is also essential for a wide range of “non-visual.
Aug 09, · Overview: Stem Cell Research at the Crossroads of Religion and Politics Embryonic stem cell research, which uses cells found in three- to five-day-old human embryos to seek cures for a host of chronic diseases, has . Stem cells are cells that can be induced to become any type of tissue.
They are thought to be the Holy Grail for researchers who are trying to develop therapies for diseases and injuries. Christians need to understand the basics of stem cell research so they can make informed decisions.
There are. Today, with the Executive Order I am about to sign, we will bring the change that so many scientists and researchers; doctors and innovators; patients and loved ones have hoped for, and fought for, these past eight years: we will lift the ban on federal funding for promising embryonic stem cell research.