Therapeutic effects of extracellular vesicles from human adipose‐derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis

Jafarinia, Morteza; Alsahebfosoul, Fereshteh; Salehi, Hossein; Eskandari, Nahid; Azimzadeh, Maryam; Mahmoodi, Merat; Asgary, S.; Ganjalikhani‐Hakemi, Mazdak

doi:10.1002/jcp.29721

Cited by 53 publications

(54 citation statements)

References 48 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, MSC exos replacing their parental MSC modulate immune functions (Baquir & Hancock, 2017; Chen et al., 2016), and consequently there is similar data as the above in models of autoimmune diseases; such as: systemic lupus (Perez‐Hernandez, Redon, & Cortes, 2017; Sharma et al., 2017; Zhou et al., 2020), the collagen sensitivity model of rheumatoid arthritis (Chen, Wang, Xia, Yan, & Lu, 2018; Li, Li, Liu, Gao, & Li, 2019). Type I diabetes mellitus (Chang & Wang, 2019; Nojehdehi et al., 2018) inflammatory bowel disease (Mao et al., 2018), and the experimental autoimmune encephalomyelitis model of multiple sclerosis (Farinazzo et al., 2018; Jafarinia, Alsahebfosoul, Salehi, & Eskandari, 2020; Riazifar et al., 2019).…”

Section: Covid 19 Therapy With Mesenchymal Stromal Cellsmentioning

confidence: 99%

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Askenase

2020

J of Extracellular Vesicle

View full text Add to dashboard Cite

Exosome extracellular vesicles as biologic therapy for COVID‐19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID‐19 patients. Instead, it is recommended to treat alternatively with their MSC‐released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID‐19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID‐19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID‐19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID‐19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID‐19 patients.

show abstract

Section: Covid 19 Therapy With Mesenchymal Stromal Cellsmentioning

confidence: 99%

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Askenase

2020

J of Extracellular Vesicle

View full text Add to dashboard Cite

show abstract

“…Human ASCs have shown considerable therapeutic ability in the EAE mouse model of MS [ 10 , 15 , 18 , 19 , 20 , 43 , 44 ]. Thus, we investigated whether a novel Rapa preconditioning approach enhanced or inhibited their immunomodulatory capacity.…”

Section: Resultsmentioning

confidence: 99%

“…Human ASCs have demonstrated robust therapeutic efficacy in preclinical models of MS [ 10 , 15 , 18 , 19 , 20 , 43 , 44 ], primarily through their immunoregulation of innate and adaptive immune cells [ 48 , 49 ]. However, clinical success with ASCs faces many challenges, including post-transplant apoptosis and weakened immunomodulatory potency [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis

Wise

Harrison

Sullivan

et al. 2020

Cells

View full text Add to dashboard Cite

Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4+ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.

show abstract

“…The treatments with EVs and AD-MSCs decreased clinical score and MOG-induced proliferation of splenocytes compared with untreated EAE control mice. In addition, inflammatory infiltrates and demyelination areas were reduced in animals treated with EVs or AD-MSCs [ 81 ].…”

Section: Mscs Secretome In Multiple Sclerosis Experimental Modelsmentioning

confidence: 99%

Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies

Gugliandolo

Bramantı

Mazzon

2020

IJMS

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Nowadays, available therapies for MS can help to manage MS course and symptoms, but new therapeutic approaches are required. Stem cell therapy using mesenchymal stem cells (MSCs) appeared promising in different neurodegenerative conditions, thanks to their beneficial capacities, including the immunomodulation ability, and to their secretome. The secretome is represented by growth factors, cytokines, and extracellular vesicles (EVs) released by MSCs. In this review, we focused on studies performed on in vivo MS models involving the administration of MSCs and on clinical trials evaluating MSCs administration. Experimental models of MS evidenced that MSCs were able to reduce inflammatory cell infiltration and disease score. Moreover, MSCs engineered to express different genes, preconditioned with different compounds, differentiated or in combination with other compounds also exerted beneficial actions in MS models, in some cases also superior to native MSCs. Secretome, both conditioned medium and EVs, also showed protective effects in MS models and appeared promising to develop new approaches. Clinical trials highlighted the safety and feasibility of MSC administration and reported some improvements, but other trials using larger cohorts of patients are needed.

show abstract

Therapeutic effects of extracellular vesicles from human adipose‐derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis

Cited by 53 publications

References 48 publications

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?

Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis

Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies

Contact Info

Product

Resources

About