Pro-elastogenic Effects of Mesenchymal Stem Cell Derived Smooth Muscle Cells in a 3D Collagenous Milieu.

Intrinsically poor auto-regenerative repair of proteolytically-disrupted elastic matrix structures by resident SMCs in the wall of abdominal aortic aneurysms (AAAs) prevents growth arrest and regression of these wall expansions.

Supporting their possible future use in a regenerative cell therapy for AAAs, in a prior study, we showed that bone marrow mesenchymal stem cell-derived Smooth Muscle Cells (BM-SMCs) secrete biological factors that have significant pro-elastogenic and anti-proteolytic effects on aneurysmal rat aortic SMCs (EaRASMCs) in non-contact co-cultures.

We also identified one stable BM-SMC phenotype (cBM-SMC) generated by differentiating BM-MSCs on a 2D fibronectin substrate in the presence of PDGF (Platelet Derived Growth Factor) and TGF-β1 (Transforming Growth Factor-β1) that exhibited superior elastogenicity and pro-elastogenic/anti-proteolytic properties.

In this study, we further investigated the ability of these cBM-SMCs to maintain these superior elastogenic properties in a 3D collagenous milieu alone and in co-culture with EaRASMC to evaluate their potential as an alternative cell source for cell therapy in AAA. Some of our key observations were higher contractility and greater amount of structurally intact elastin production in both standalone culture of cBM-SMCs as well as co-culture of cBM-SMCs with EaRASMCs as shown by VVG (Verhoeff-Van Gieson) staining and Pontamine Sky Blue labeling and lower MMP-9 protein expression in standalone culture in 3D collagenous environment.

Our overall result indicate that cBM-SMCs possess the ability to provide elastogenic impetus in a 3D collagenous AAA milieu which is otherwise not conducive to elastogenesis.

Therefore our study strongly suggest the utility of cBM-SMCs as a potential cell source for cell therapy to augment elastic matrix neo-assembly and fiber formation and attenuate proteolysis in a collagenous milieu that is evocative of the de-elasticized aneurysmal wall.