Targeting Adult Stem Cell-Derived Smooth Muscle Cells to the Aortal Wall for Augmented ECM Repair

摘要

Statement of Purpose: Adult bone marrow mesenchymal stem cells (BM-MSCs) therapy for tissue regenerative repair is a paradigm shifting technology that is being widely investigated over past several years. BM-MSCs have the potential to differentiate into different phenotypes and they also secrete a variety of cytokines and growth factors that have paracrine activities to leverage them for tissue regenerative repair. We have extensively published on differentiating BM-MSCs into Smooth Muscle Cells (BM-SMCs) phenotype, modulating the phenotype based on differentiation condition, assessing their elastogenicity, pro-elastogenic effects and anti-proteolytic activities in both 2D and in-vivo like 3D cultures towards their utility as an alternative cell source for cell therapy for regressing abdominal aortic aneurysms (AAAs) growth.Effectiveness of cell therapy largely relies on methods of cell delivery, bio-distribution of cells post-delivery and the ability of cells to home-in and be retained in the target site to impart desired benefits. Hence, this study is focused on observing the natural homing ability of specific stem cell-derivative (cBM-SMCs) that we have previously characterized in-vitro for their use in AAAs. The homing of MSCs is facilitated by expression of chemokine receptors primarily CXCR4 and CCR3 towards their ligand Stromal Derived Factor-1 (SDF-1) which is overexpressed in the injury site. We hypothesize that cBM-SMCs, being derived from BM-MSCs, also express these homing receptors and the expression is further enhanced by stimulating them with cytokine like TNF-α. Besides this, we are interested in investigating their bio-distribution in our elastase infused rat AAA model where we will be tagging the cells with a contrast agent called Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) and deliver these SPIONs tagged cells via tail-vein injection to visualize them with MRI.