Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles
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Journal of Nanobiotechnology Open Access
RESEARCH
Improvement of stem cell‑derived exosome release efficiency by surface‑modified nanoparticles Dong Jun Park1,2, Wan Su Yun3, Woo Cheol Kim3, Jeong‑Eun Park1,2, Su Hoon Lee1,2, Sunmok Ha4, Jin Sil Choi1,2, Jaehong Key3 and Young Joon Seo1,2*
Abstract Background: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSCderived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. Results: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We deter‑ mined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. Conclusions: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrinmediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors. Keywords: Autophagy, Mesenchymal stem cell-derived exosome, Positively charged nanoparticle, PLGA-PEI NPs, Rab7 Background Therapeutic clinical studies using mesenchymal stem cells (MSCs) have been recently reported, and techniques using MSC-derived exosomes are being actively developed. Several studies have explored the application of cell-derived exosomes for medical purposes. For example, MSC-derived exosomes have been used to suppress immune responses or as a therapeutic treatment for cancer [1, 2]. In cell-free therapies, to increase the quantity *Correspondence: [email protected] 1 Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, 20 Ilsan‑ro, Wonju, Gangwon‑do 26426, South Korea Full list of author information is available at the end of the article
of exosomes, biocompatible materials are now being used [3, 4]. However, the protocols for obtaining a consistent yield and an efficient exosome extraction process for medical use have not been established yet. The yield of exosomes derived from stem cells is very low, which warrants optimization of conditions to increase yields. Sucrose gradient-based ultra-centrifugation is commonly used to obtain materials for various applications [5–7]. Extracellular vesicles (EVs) play an important role in cell-to-cell communication through the delivery of biological content, including intercellular proteins, lipids, and nucleic acids. Nanoscale EVs are difficult to maintain their mo
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