The Study of BD-MSC Therapy against Critical Limb Ischemia / 체질인류학회지

ABSTRACT

Critical limb ischemia (CLI) is the most severe peripheral artery disease and caused by thrombus formation in blood vessel. The current strategies for treating CLI does not protect limb amputation and reduction in the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (BD-MSC) were reported to have a paracrine effects on angiogenesis in several ischemic diseases. So, we validate to determine whether BD-MSC protect against ferric chloride treated CLI and induce angiogenesis. To characterized human bone marrow derived stem cell, BD-MSC differentiated to osteocytes and adipocytes and validated stemness using flow cytometry. Endothelial cell induced angiogenesis followed by mesenchymal stem cell cultured medium treatment in HUVEC in vitro. We also mimicked CLI patients condition using FeCl₃ treated CLI mouse and injected one hundred thousand of BD-MSC along the femoral artery to leg muscle. We validated stem cell survival, blood vessel formation, leg muscle condition and fibrosis compared by saline injected mice 28 days later. In this study, BD-MSC cultured medium treatment increased migration and tube formation of HUVEC and BD-MSC injection had an effective blood vessel formation in FeCl₃ treated CLI. As well as blood vessel formation, limb salvage rate also improved and fibrosis area statistically decreased in BD-MSC injected mice. In conclusion, bone marrow derived mesenchymal stem cell improved not only blood vessel formation but also reduction of fibrosis in FeCl₃ treated CLI mice and finally protected limb amputation.