Premium
Induced Pluripotent Stem Cells (iPS)‐Derived Extracellular Vesicles Improves Immune Dysfunction and Attenuates Splenomegaly in Aged Mice
Author(s) -
Ullah Mujib,
Feng Rui,
Sun Zhongjie
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.753.6
Subject(s) - immune system , inflammation , immunosenescence , proinflammatory cytokine , immunology , spleen , t cell , medicine , biology
Background and Objective Aging is associated with declined immune function and increased inflammatory responses. Secreted extracellular vesicles (EVs) are loaded with growth factors, cytokines, and miRNAs. The purpose of this study is to investigate the effect of intravenous delivery of iPS cell‐derived EVs on the aging‐associated immune dysfunction. Methods and Results The iPS cell‐derived EVs was confirmed by the expression of CD9, CD63 and CD83. The populations of T and B lymphocytes were decreased in aged mice, indicating that aging impairs the immune function. Intravenous delivery of EVs rescued the aging‐related decrease in immune cell populations. The size and weight of spleens were increased in aged mice, suggesting that aging causes spleen hypertrophy (splenomegaly). We found that the aging‐related splenomegaly was accompanied by increased cell death, necrosis, unbalanced ratio of immune cells, and augmented inflammation. Immunosenescence, cell arrest, apoptosis, fibrosis and iron accumulation was also found in the hypertrophied spleens of aged mice. Interestingly, EVs significantly attenuated aging‐associated splenomegaly, immunosenescence, cell arrest, apoptosis, and spleen remodeling. Aging enhanced inflammation as evidenced by increased immune cells and proinflammatory cytokines (IL‐1β, IL‐18, TNF‐α) in aged mice. iPS cell‐derived EVs markedly reduced inflammation, improved population of B and T cells, and increased anti‐inflammatory cytokines (IL‐4, IL‐6, IL‐10, IL‐13, TGF‐β) in aged mice. In comparison with EVs alone, EVs overexpressing klotho protein (an antiaging protein) more effectively enhanced the immune function and suppressed inflammation in aged mice. Conclusions These results showed for the first time that EVs alone or in combination with klotho overexpression suppressed aging‐associated inflammation and splenocyte apoptosis likely via modulating the immune function. EVs may be a promising interventional strategy for aging‐related immune dysfunction and splenomegaly. Support or Funding Information NIH R01 AG049780, HL118558, AND DK093403. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .