Adventitial pericyte progenitor/mesenchymal stem cells participate in the restenotic response to arterial injury

Restenosis is a major complication of coronary angioplasty, at least partly due to the fact that the origin and identity of contributing cell types are not well understood. In this study, we have investigated whether pericyte-like cells or mesenchymal stem cells (MSCs) from the adventitia contribute to restenosis. We demonstrate that while cells expressing the pericyte markers NG2, platelet-derived growth factor receptor β, and CD146 are rare in the adventitia of uninjured mouse femoral arteries, following injury their numbers strongly increase. Some of these adventitial pericyte-like cells acquire a more MSC-like phenotype (CD90+ and CD29+ are up-regulated) and also appear in the restenotic neointima. Via bone marrow transplantation and ex vivo artery culture approaches, we demonstrate that the pericyte-like MSCs of the injured femoral artery are not derived from the bone marrow, but originate in the adventitia itself mainly via the proliferation of resident pericyte-like cells. In summary, we have identified a population of resident adventitial pericyte-like cells or MSCs that contribute to restenosis following arterial injury. These cells are different from myofibroblasts, smooth muscle cells, and other progenitor populations that have been shown to participate in the restenotic process.