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Derivation of Cell-Engineered Nanovesicles from Human Induced Pluripotent Stem Cells and Their Protective Effect on the Senescence of Dermal Fibroblasts

Department of Medical Biomaterials Engineering, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do 24341, Korea
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Int. J. Mol. Sci. 2020, 21(1), 343; https://doi.org/10.3390/ijms21010343
Received: 8 November 2019 / Revised: 20 December 2019 / Accepted: 2 January 2020 / Published: 5 January 2020
(This article belongs to the Section Biochemistry)
Stem cells secrete numerous paracrine factors, such as cytokines, growth factors, and extracellular vesicles. As a kind of extracellular vesicle (EV), exosomes produced in the endosomal compartment of eukaryotic cells have recently emerged as a biomedical material for regenerative medicine, because they contain many valuable contents that are derived from the host cells, and can stably deliver those contents to other recipient cells. Although we have previously demonstrated the beneficial effects of human induced potent stem cell-derived exosomes (iPSC-Exo) on the aging of skin fibroblasts, low production yield has remained an obstacle for clinical applications. In this study, we generated cell-engineered nanovesicles (CENVs) by serial extrusion of human iPSCs through membrane filters with diminishing pore sizes, and explored whether the iPSC-CENV ameliorates physiological alterations of human dermal fibroblasts (HDFs) that occur by natural senescence. The iPSC-CENV exhibited similar characteristics to the iPSC-Exo, while the production yield was drastically increased compared to that of iPSC-derived EVs, including exosomes. The proliferation and migration of both young and senescent HDFs were stimulated by the treatment with iPSC-CENVs. In addition, it was revealed that the iPSC-CNEV restored senescence-related alterations of gene expression. Treatment with iPSC-CENVs significantly reduced the activity of senescence-associated-β-galactosidase (SA-β-Gal) in senescent HDFs, as well as suppressing the elevated expression of p53 and p21, key factors involved in cell cycle arrest, apoptosis, and cellular senescence signaling pathways. Taken together, these results suggest that iPSC-CENV could provide an excellent alternative to iPSC-exo, and be exploited as a resource for the treatment of signs of skin aging. View Full-Text
Keywords: cell-engineered nanovesicle (CENV); human induced pluripotent stem cell (iPSC); cellular senescence; skin aging cell-engineered nanovesicle (CENV); human induced pluripotent stem cell (iPSC); cellular senescence; skin aging
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MDPI and ACS Style

Lee, H.; Cha, H.; Park, J.H. Derivation of Cell-Engineered Nanovesicles from Human Induced Pluripotent Stem Cells and Their Protective Effect on the Senescence of Dermal Fibroblasts. Int. J. Mol. Sci. 2020, 21, 343. https://doi.org/10.3390/ijms21010343

AMA Style

Lee H, Cha H, Park JH. Derivation of Cell-Engineered Nanovesicles from Human Induced Pluripotent Stem Cells and Their Protective Effect on the Senescence of Dermal Fibroblasts. International Journal of Molecular Sciences. 2020; 21(1):343. https://doi.org/10.3390/ijms21010343

Chicago/Turabian Style

Lee, Hyelim, Hyeonjin Cha, and Ju H. Park 2020. "Derivation of Cell-Engineered Nanovesicles from Human Induced Pluripotent Stem Cells and Their Protective Effect on the Senescence of Dermal Fibroblasts" International Journal of Molecular Sciences 21, no. 1: 343. https://doi.org/10.3390/ijms21010343

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