Genetic lineage tracing analysis of c-kit+ stem/progenitor cells revealed a contribution to vascular injury-induced neointimal lesions.
J Mol Cell Cardiol
; 121: 277-286, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-30053526
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artérias
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Células-Tronco
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Túnica Íntima
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Proteínas Proto-Oncogênicas c-kit
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Linhagem da Célula
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China