| Elastic fibers (EFs), containing elastin protein are the major structural extracellular matrix component of the aorta wall that imparts it stretch and recoil properties. Following injury stimuli to the aorta wall, EFs are disrupted by chronically overexpressed proteolytic enzymes. This leads to loss of wall elasticity, and vessel bulging to form rupture-prone abdominal aortic aneurysms (AAAs). AAA growth arrest or regression to a healthy state requires restoration of elastin homeostasis in the aorta wall which is limited by very poor elastogenicity of adult and aneurysmal vascular smooth muscle cells (SMCs). Based on their purported role in developmental elastogenesis, we explored use of stem cell-derived SMCs in therapeutically augmenting elastogenesis in the AAA wall. In study 1, we differentiated adult rat bone marrow mesenchymal stem cells (BM-MSCs) into SMCs (BM-SMCs), demonstrated their robust capacity for elastin synthesis and significant pro-elastogenic effects on rat aneurysmal SMCs (EaRASMCs). In study 2, we sought to identify phenotypic subtypes of derived BM-SMCs that are most elastogenic. BM-SMCs generated in low glucose (3.1g/L) and high serum (10% v/v) media containing transforming growth factor-beta (TGF&... |
