Exosomal miR‐146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin‐1β‐Primed Mesenchymal Stem Cells Against Sepsis
Yuxian Song,Dou Huan,Xiujun Li,Zhao Xiaoyin,Yi Li,Dan Liu,Jianjian Ji,Fei Liu,Liang Ding,Ni Yanhong,Yayi Hou +10 more
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TLDR
It is found that systemic administration of IL‐1β‐pretreated MSCs (βMSCs) is found to be ameliorated the symptoms of murine sepsis more effectively and increased the survival rate compared with naïve M SCs, and it is believed that IL‐ 1β pretreatment may provide a new modality for better therapeutic application of MSCS in inflammatory disorders.Abstract:
Improving the immunomodulatory efficacy of mesenchymal stem cells (MSCs) through pretreatment with pro-inflammatory cytokines is an evolving field of investigation. However, the underlying mechanisms have not been fully clarified. Here, we pretreated human umbilical cord-derived MSCs with interleukin-1β (IL-1β) and evaluated their therapeutic effects in a cecal ligation and puncture-induced sepsis model. We found that systemic administration of IL-1β-pretreated MSCs (βMSCs) ameliorated the symptoms of murine sepsis more effectively and increased the survival rate compared with naive MSCs. Furthermore, βMSCs could more effectively induce macrophage polarization toward an anti-inflammatory M2 phenotype through the paracrine activity. Mechanistically, we demonstrated that βMSC-derived exosomes contributed to the enhanced immunomodulatory properties of βMSCs both in vitro and in vivo. Importantly, we found that miR-146a, a well-known anti-inflammatory microRNA, was strongly upregulated by IL-1β stimulation and selectively packaged into exosomes. This exosomal miR-146a was transferred to macrophages, resulted in M2 polarization, and finally led to increased survival in septic mice. In contrast, inhibition of miR-146a through transfection with miR-146a inhibitors partially negated the immunomodulatory properties of βMSC-derived exosomes. Taken together, IL-1β pretreatment effectively enhanced the immunomodulatory properties of MSCs partially through exosome-mediated transfer of miR-146a. Therefore, we believe that IL-1β pretreatment may provide a new modality for better therapeutic application of MSCs in inflammatory disorders. Stem Cells 2017;35:1208-1221.read more
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Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19
Jing Ren,Liang Ding,Dongya Zhang,Guoping Shi,Qianyun Xu,Sunan Shen,Yaping Wang,Tingting Wang,Yayi Hou +8 more
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Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization
TL;DR: The data indicate that MSC-Exo attenuates myocardial I/R injury in mice via shuttling miR-182 that modifies the polarization status of macrophages.
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Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis
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MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis.
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Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders.
Milad Riazifar,M. Rezaa Mohammadi,Egest J. Pone,Ashish Yeri,Cecilia Lässer,Aude I. Segaliny,Laura L. McIntyre,Ganesh Vilas Shelke,Ganesh Vilas Shelke,Elizabeth Hutchins,Ashley Hamamoto,Erika N. Calle,Rossella Crescitelli,Wenbin Liao,Victor Pham,Yanan Yin,Jayapriya Jayaraman,Jonathan R. T. Lakey,Craig M. Walsh,Kendall Van Keuren-Jensen,Jan Lötvall,Weian Zhao +21 more
TL;DR: Evidence is provided that MSC-derived exosomes can potentially serve as cell-free therapies in creating a tolerogenic immune response to treat autoimmune and central nervous system disorders and that IFNγ-Exo harbors multiple anti-inflammatory and neuroprotective proteins.
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