Genetic lineage tracing analysis of c-kit+ stem/progenitor cells revealed a contribution to vascular injury-induced neointimal lesions. (August 2018)

• Record Type: Journal Article
• Authors: Chen, Qishan; Yang, Mei; Wu, Hong; Zhou, Jiaojiao; Wang, Weina; Zhang, Hongkun; Zhao, Lin; Zhu, Jianhua; Zhou, Bin; Xu, Qingbo; Zhang, Li
• Is Part Of: Journal of molecular and cellular cardiology. Volume 121(2018)
• Page Start: 277
• Page End: 286
• Publication Date: 2018-08
• Subjects: Cell lineage tracing -- C-kit+ progenitor -- Endothelial cell -- Smooth muscle cell -- Myeloid cell -- Neointma formation; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2018.07.252
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Aims: Accumulating evidence indicates the presence of vascular stem/progenitor cells that may play a role in endothelial repair and lesion formation in the injured artery, in which c-kit + stem/progenitor cells have been reported to differentiate into endothelial and smooth muscle cells in vitro and in ischemic tissue. In this study, we investigated whether and how endogenous 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 + stem/progenitor 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 immuno-inflammatory response to endothelial injury. Although c-kit + cells reside in both bone marrow and vessel wall, bone marrow transplantation data indicate that bone marrow-derived c-kit + cells are the 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 injury, but a plausible interventional approach to reduce vascular immuno-inflammatory response and subsequently to ameliorate vascular lesions. Highlights: Endogenous c-kit+ stem/progenitor cells minimally differentiate into endothelial and smooth muscle cells in repairing of large arteries. Endogenous c-kit+ stem/progenitor cells predominantly generate immuno-inflammatory cells in response to endothelial injury. Depleting c-kit+ stem/progenitor cells and their immuno-inflammatory progeny may be a therapeutic approach to be combined with CABG or stent technologies in intervention.