Abstract 18045: Stem Cell Impregnated Nanofiber Stent Sleeve for Intravascular Paracrine Factor Production

Abstract

Background: Results of stem cell studies for cardiomyopathy and peripheral artery disease are promising, but benefits remain modest in part due to cell washout and immune attack. Evidence suggests that many stem cell effects are paracrine-mediated, wherein secreted factors activate intrinsic repair. We now describe a stem cell impregnated nanofiber (NF) stent sleeve in which a biodegradable NF sleeve is electrospun around a stent and impregnated with a large number of stem cells. The porous sleeve nanostructure prevents cell washout and immune attack, and allows sustained local production and secretion of stem cell paracrine factors. Methods: NF stent sleeves are created by electrospinning poly-lactic-co-glycolic acid (PLGA) co-polymer onto expanded stents. Sleeves are impregnated with stem cells in a 1.2 mL solution of 3.2x10 6 mesenchymal stem cells (MSCs). Sleeve nanostructure was examined by electron microscopy. MSC adhesion and viability in the sleeve were assessed on days 1 and 8 using a fluorescent cell viability assay. VEGF and HGF secretion was quantified by ELISA over 7 days. Biological activity of sleeves with MSCs was determined by HUVEC tubule formation on day 8 and compared to sleeves without MSCs. Results: Stent sleeves consist of randomly oriented NFs (A) uniformly covering the stent (B) onto which MSCs readily attached. MSCs proliferated normally, remained CD90+ and CD44+, and were confluent on day 8 (C,D) with more than 90% viability. VEGF and HGF (E,F) continued to be secreted, and sleeves with MSCs induced HUVECs to organize into tubules to a 3.1±0.7 fold greater extent than control. NF sleeves can be crimped onto angioplasty balloons and delivered via 8F catheters. Conclusion: Our results demonstrate the engineering feasibility of a stem cell impregnated NF stent sleeve, and pave the way for animal studies to assess the efficacy of local paracrine factor production and delivery to treat cardiomyopathy and peripheral artery disease.