Human Umbilical Cord Mesenchymal Stem Cells Attenuate Abdominal Aortic Aneurysm Progression in Sprague Dawley Rats: Implication of Vascular Smooth Muscle Cell Phenotypic Modulation

Abdominal aortic aneurysm (AAA) is life-threatening for which efficient non-surgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSC) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix (ECM) destruction, suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSC on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSC) in elastase induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuate elastase induced aneurysmal expansion, reduce elastin degradation and fragmentation, inhibit MMPs and TNF-α expression, preserve and/or restore VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.