AUTHOR=Ben Xin-Yu , Wang Ya-Ru , Zheng Hui-Hui , Li De-Xian , Ren Rui , Ni Pan-Li , Zhang Hai-Ying , Feng Ren-Jun , Li Yun-Qing , Li Qi-Fu , Yi Xi-Nan 

TITLE=Construction of Exosomes that Overexpress CD47 and Evaluation of Their Immune Escape

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.936951

DOI=10.3389/fbioe.2022.936951

ISSN=2296-4185

ABSTRACT=<p>Our general purpose was to provide a theoretical and practical foundation for the use of exosomes (EXOs) that have high levels of CD47 as stable and efficient drug carriers. Thus, we prepared EXOs from adipose tissue-derived mesenchymal stromal cells (ADMSCs) that had high levels of CD47 (EXOs<sup>CD47</sup>) and control EXOs (without CD47), and then compared their immune escape <italic>in vivo</italic> and their resistance to phagocytosis <italic>in vitro</italic>. Nanoflow cytometry was used to determine the CD47 level in these EXOs, and the amount of EXOs<sup>CD47</sup> that remained in rat plasma at 3 h after intraperitoneal injection. Phagocytosis of the EXOs was also determined using <italic>in vitro</italic> rat macrophage bone marrow (RMA-BM) experiments. Our <italic>in vitro</italic> results showed that macrophages ingested significantly more control EXOs than EXOs<sup>CD47</sup> (<italic>p</italic> &lt; 0.01), with confirmation by ultra-high-definition laser confocal microscopy. Consistently, our <italic>in vivo</italic> results showed that rats had 1.377-fold better retention of EXOs<sup>CD47</sup> than control EXOs (<italic>p</italic> &lt; 0.01). These results confirmed that these engineered EXOs<sup>CD47</sup> had improved immune escape. Our results therefore verified that EXOs<sup>CD47</sup> had increased immune evasion relative to control EXOs, and have potential for use as drug carriers.</p>