Magnetically Responsive Bone Marrow Mesenchymal Stem Cell-Derived Smooth Muscle Cells Maintain Their Benefits to Augmenting Elastic Matrix Neoassembly

Abstract

Abdominal aortic aneurysms (AAA) represent abnormal aortal expansions that result from chronic proteolytic breakdown of elastin and collagen fibers by matrix metalloproteases. Poor elastogenesis by adult vascular smooth muscle cells (SMCs) limits regenerative repair of elastic fibers, critical for AAA growth arrest. Toward overcoming these limitations, we recently demonstrated significant elastogenesis by bone marrow mesenchymal stem cell-derived SMCs (BM-SMCs) and their proelastogenesis and antiproteolytic effects on rat aneurysmal SMCs (EaRASMCs). We currently investigate the effects of super paramagnetic iron oxide nanoparticle (SPION) labeling of BM-SMCs, necessary to magnetically guide them to the AAA wall, on their functional benefits. Our results indicate that SPION-labeling is noncytotoxic and does not adversely impact the phenotype and elastogenesis by BM-SMCs. In addition, SPION-BM-SMCs showed no changes in the ability of the BM-SMCs to stimulate elastin regeneration and attenuate proteolytic activity by EaRASMCs. Together, our results are promising toward the utility of SPIONs for magnetic targeting of BM-SMCs for in situ AAA regenerative repair.

Hypoxia Stimulates Synthesis of Neutrophil Gelatinase-Associated Lipocalin in Aortic Valve Disease

“…After 1 week in culture, porcine AV leaflets were harvested for protein isolation as described previously (17, 18). Briefly, the leaflets were flash frozen with liquid nitrogen and stored at −80°C overnight before being lyophilized for 24 h. The lyophilized tissues were harvested in T-PER lysis buffer (Thermo Fisher Scientific) containing 1% Halt™ protease inhibitor cocktail (Thermo Fisher Scientific) and homogenized using a Tissue Lyser II (Qiagen, Germantown, MD).…”

“…The effect of hypoxia on the enzyme activity of MMPs 2 and 9 was analyzed using gel zymography (18, 20). A total of 10 and 4 μg of tissue and cell lysates, respectively, were loaded in each lane of 10% gelatin zymogram gels (Invitrogen) and run for 2 h at 125 V. Subsequently, the gels were washed with 2.5% v/v TritonX-100 for 30 min, incubated in substrate development buffer (G Biosciences, St. Louis, MO) for 48 h, stained with Coomassie Brilliant Blue (Bio-Rad), and de-stained with water until clear bands were visible.…”

Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review

“…74 The authors did not register any adverse impact of the SPIONs on the cells' viability, phenotype, elastic matrix synthesis, and elastogenesis-stimulatory and antiproteolytic properties and concluded that this can be a very useful approach for in situ AAA regenerative repair.…”

Nanotherapeutics to Modulate the Compromised Micro-Environment for Lung Cancers and Chronic Obstructive Pulmonary Disease

“…NPs can also be conjugated to the cell membrane of MSCs to ensure cell survival toward subsequent tumor inhibition ( Li et al, 2011 ). SMCs have aided in ECM regeneration and can be a worthwhile delivery vehicle to target the alveoli to regenerate the elastic matrix ( Swaminathan et al, 2016 ). Our lab has recently demonstrated significant elastogenesis by bone marrow MSC-derived SMC-like cells (BM-SMCs) and their pro-elastogenic and anti-proteolytic effects on rat aneurysmal SMCs.…”

“…Our lab has recently demonstrated significant elastogenesis by bone marrow MSC-derived SMC-like cells (BM-SMCs) and their pro-elastogenic and anti-proteolytic effects on rat aneurysmal SMCs. The BM-SMCs were loaded with super paramagnetic iron oxide nanoparticles (SPIONs) toward guiding them to the AAA wall using an applied external magnetic field ( Swaminathan et al, 2016 ). In vitro , the BM-SMCs stimulated elastin regeneration and attenuated proteolytic activity by cocultured aneurysmal SMCs both upon and without SPION labeling.…”