In vivo Tracking and Effects of SPIO‐labeled Mesenchymal Stem Cells in a Porcine Model of Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) pathogenesis involves extracellular matrix remodeling, degeneration, and inflammation, making it a promising target for cell‐based therapy. This study demonstrates, in a large animal model, the feasibility of tracking implanted mesenchymal stem cells (MSC) on in vivo MRI with Superparamagnetic Iron Oxide (SPIO) labeling and then characterizing potential reparative effects.Dosimetry and cell viability experiments with SPIO were performed on porcine BM‐MSCs. Tracking of SPIO‐labeled MSCs was performed with 3T MRI. Histological changes in iron, elastin, collagen, and smooth muscle actin were assessed, and levels of inflammatory markers were quantified using RT‐PCR.Optimal imaging and cell viability were achieved with SPIO conc of 500ug/mL. SPIO‐labeled MSCs demonstrated positive CD90 and negative CD45 markers, consistent with the MSC phenotype. MRI tracking demonstrated circumferential migration of the implanted MSCs. Histological analysis demonstrated an increase in collagen, elastin, and smooth muscle cell synthesis in treatment groups compared to controls, as well as mild decrease in inflammatory markers such as MMPs ‐2, ‐3, ‐9, IL‐1B, and TNF‐alpha.MSCs can be successfully labeled, implanted, and tracked by in vivo MRI in a large animal model of AAA. The MSCs may stabilize AAA degeneration through the production of new collagen, elastin, and smooth muscle cells, as well as decreasing inflammation.