Engineered exosomes reprogram Gli1 <sup>+</sup> cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels
Juan Yan, Haoran Xiao, Xin Zhou, Yanzhao Li, Shanlan Zhao, Xingli Zhao, Yong Liu, Min Liu, Fangchao Xue, Qiao Zhang, Wenyan Zhao, Lang Li, Yang Su, Wen Zeng
Abstract
Calcification of autologous pathological vessels and tissue engineering blood vessels (TEBVs) is a thorny problem in clinic. However, there is no effective and noninvasive treatment that is available against the calcification of TEBVs and autologous pathological vessels. Gli1 + cells are progenitors of smooth muscle cells (SMCs) and can differentiate into osteoblast-like cells, leading to vascular calcification. Our results showed that the spatiotemporal distribution of Gli1 + cells in TEBVs was positively correlated with the degree of TEBV calcification. An anticalcification approach was designed consisting of exosomes derived from mesenchymal stem cells delivering lncRNA-ANCR to construct the engineered exosome-Ancr/E7-EXO. The results showed that Ancr/E7-EXO effectively targeted Gli1 + cells, promoting rapid SMC reconstruction and markedly inhibiting Gli1 + cell differentiation into osteoblast-like cells. Moreover, Ancr/E7-EXO significantly inhibited vascular calcification caused by chronic kidney disease. Therefore, Ancr/E7-EXO reprogrammed Gli1 + cells to prevent calcification of vascular graft and autologous pathological vessel, providing unique insights for an effective anticalcification.