Potential role of vascular smooth muscle cell-like progenitor cell therapy in the suppression of experimental abdominal aortic aneurysms

Abstract

Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.