Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review

BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

Mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles:Potential roles in rheumatic diseases

BACKGROUND Mesenchymal stem cells(MSCs)have been widely investigated in rheumatic disease due to their immunomodulatory and regenerative properties.Recently,mounting studies have implicated the therapeutic potency of MSCs mostly due to the bioactive factors they produce.Extracellular vesicles(EVs)derived from MSCs have been identified as a promising cell-free therapy due to low immunogenicity.Rheumatic disease,primarily including rheumatoid arthritis and osteoarthritis,is a group of diseases in which immune dysregulation and chronic progressive inflammation lead to irreversible joint damage.Targeting MSCs and MSC-derived EVs may be a more effective and promising therapeutic strategy for rheumatic diseases.AIM To evaluate the potential therapeutic effectiveness of MSCs and EVs generated from MSCs in rheumatic diseases.METHODS PubMed was searched for the relevant literature using corresponding search terms alone or in combination.Papers published in English language from January 1999 to February 2020 were considered.Preliminary screening of papers concerning analysis of"immunomodulatory function"or"regenerative function"by scrutinizing the titles and abstracts of the literature,excluded the papers not related to the subject of the article.Some other related studies were obtained by manually retrieving the reference lists of papers that comply with the selection criteria,and these studies were screened to meet the final selection and exclusion criteria.RESULTS Eighty-six papers were ultimately selected for analysis.After analysis of the literature,it was found that both MSCs and EVs generated from MSCs have great potential in multiple rheumatic diseases,such as rheumatoid arthritis and osteoarthritis,in repair and regeneration of tissues,inhibition of inflammatory response,and regulation of body immunity via promoting chondrogenesis,regulating innate and adaptive immune cells,and regulating the secretion of inflammatory factors.But EVs from MSCs exhibit much more advantages over MSCs,which may represent another promising cell-free restorative strategy.Targeting MSCs and MSC-derived EVs may be a more efficient treatment for patients with rheumatic diseases.CONCLUSION The enormous potential of MSCs and EVs from MSCs in immunomodulation and tissue regeneration offers a new idea for the treatment of rheumatism.However,more in-depth exploration is needed before their clinical application.