Abstract No. 31 Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia in a Rat Model of Arteriovenous Fistula

A wide array of perivascular interventions have shown potential in improving arteriovenous fistula (AVF) maturation by providing a direct therapeutic effect against neointimal hyperplasia (NIH), a major culprit of AVF failure. These interventions include supportive mechanical devices and cell-based therapies, such as the use of mesenchymal stem cells (MSCs) that can release immunomodulatory substances and, hence, suppress NIH. However, the clearance of MSCs from the delivery site remains a challenge. Hence, we combined two perivascular interventions by fabricating an electrospun scaffold from polycaprolactone (PCL) that could support the proliferation of MSCs at the delivery site while providing mechanical support to the maturing AVF. We developed an AVF in a chronic kidney disease model by performing a 5/6 nephrectomy on Sprague-Dawley rats followed by AVF creation and perivascular scaffold application. We then compared the effect of the absence of a scaffold, a PCL scaffold alone, and an MSC-loaded PCL scaffold on AVF maturation and patency using ultrasonography (US), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), and histomorphometry. On US, both PCL and PCL+MSC significantly reduced wall thickness, increased luminal diameter, reduced wall-to-lumen ratio, and increased flow rate, but PCL+MSC resulted in a greater improvement in luminal diameter and flow rate compared with PCL alone (Table 1). Moreover, PET showed that only PCL+MSC resulted in a significant reduction in 18F-FDG uptake. On histology, both PCL and PCL+MSC significantly reduced the AVFs’ neointima-to-lumen and neointima-to-media ratios. In vivo imaging suggests that the addition of MSCs promotes better luminal expansion and blood flow and could potentially reduce the inflammatory process that underlies NIH. Overall, our results support the use of a perivascular scaffold in maximizing the utility of MSCs against NIH.