Inactivation of Vascular Stem Cells Suppresses Intimal Hyperplasia in Vein Grafts

Abstract

Chronic vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia characterized by abnormal proliferation and accumulation of vascular smooth muscle cells (SMCs), which are derived predominantly from pre-existing vascular SMCs via a process of vascular SMC dedifferentiation.1 Therapeutic approaches focused on vascular SMCs, however, have not changed chronic VGF rates,2 indicating additional and yet unrecognized causes of chronic VGF. Herein, we uncover a novel diagram in which after transplantation, recipient vascular stem cells (VSCs) expressing Sca1 are activated and accumulated in the adventitia of VGs, and they do not differentiate into SMCs but promote intimal hyperplasia via paracrine enforcement of medial SMC dedifferentiation into synthetic SMCs in VGs, suggesting that VSCs may be a novel target for the treatment of chronic VGF.