Engineered exosomes reprogram Gli1⁺ cells in vivo to prevent calcification of vascular grafts and autologous pathological vessels.

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 <i>lncRNA-ANCR</i> 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.