Abstract 18077: Lineage Tracing Analysis of c-kit+ Stem/Progenitor Cells Revealed a Contribution to Vascular Injury-Induced Neointimal Lesions

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Introduction: Accumulating evidence indicates the presence of vascular stem/progenitor cells that may play a role in endothelial repair and lesion formation in injured artery, in which c-kit+ stem/progenitor cells have been reported to differentiate into endothelial and smooth muscle cells in vitro and in infarcted heart.

Objective: To investigate whether and how c-kit+ stem/progenitor cells contribute to vascular injury and neointima formation in vivo.

Methods and Results: we created Kit-CreERxRosa26-RFP mice and performed genetic lineage tracing analysis of c-kit+ cells in injury-induced neointima formation in vivo. We provide direct evidence that endogenous c-kit+ stem/progenitor cells minimally differentiate into endothelial or smooth muscle cells facilitating vascular repair, but predominantly generate monocytes/macrophages and granulocytes contributing to vascular inflammation in response to endothelial injury. Although c-kit+ cells reside in both bone marrow and vessel wall, bone marrow transplatation data indicate that bone marrow-derived c-kit+ cells are a main source for enhancing neointima formation. Furthermore, treatment of ACK2, a c-kit receptor antagonizer, attenuates neointimal hyperplasia after injury at least in part by depleting c-kit+ cells and their generated progeny.

Conclusions: c-kit+ stem/progenitor cells are not a main source for endothelial regeneration and smooth muscle accumulation of the large artery, but a therapeutic target to reduce vascular inflammation and subsequently to ameliorate vascular lesions.

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