Vascular Stem/Progenitor Cells in Vessel Injury and Repair

Abstract

Vascular repair upon vessel injury is essential for the maintenance of arterial homeostasis and function. Stem/progenitor cells were demonstrated to play a crucial role in regeneration and replenishment of damaged vascular cells during vascular repair. Previous studies revealed that myeloid stem/progenitor cells were the main sources of tissue regeneration after vascular injury. However, accumulating evidences from developing lineage tracing studies indicate that various populations of vessel-resident stem/progenitor cells play specific roles in different process of vessel injury and repair. In response to shear stress, inflammation, or other risk factors-induced vascular injury, these vascular stem/progenitor cells can be activated and consequently differentiate into different types of vascular wall cells to participate in vascular repair. In this review, mechanisms that contribute to stem/progenitor cell differentiation and vascular repair are described. Targeting these mechanisms has potential to improve outcome of diseases that are characterized by vascular injury, such as atherosclerosis, hypertension, restenosis, and aortic aneurysm/dissection. Future studies on potential stem cell-based therapy are also highlighted.

Keywords: aortic aneurysm; atherosclerosis; hypertension; restenosis; vascular injury; vascular remodeling; vascular stem cells.

Figure 1

The distribution of cells in vascular wall. The vascular wall consists of three layers: intima, media, and adventitia. The intima consists of ECs and some vascular stem cells such as c-kit⁺ cells. The media is composed of SMCs. The adventitia is composed of vascular stem cells (Sca-1⁺ cells, c-kit⁺ cells, CD34⁺ cells, pericytes, etc.) and fibroblasts.

Figure 2

The differentiation signaling pathway of vascular progenitor cells. Vascular development and remodeling depend on many genes and are usually initiated by fluid shear stress which acts on the Notch signaling and closely associated with the vascular remodeling diseases. DKK3 induces ECs migration through Wnt-PCP signaling pathway, accelerating re-endothelialization, and reducing neointima formation. DKK3 can induce the differentiation of Sca-1+ progenitor cells and fibroblasts into VSMC by activating TGF-β/ATF6 signaling pathways.

Figure 3

The different roles in vascular remodeling diseases of vascular progenitor cells. c-Kit⁺ cells can differentiate into ECs and participate in endothelial homeostasis. Sca-1⁺ progenitor cells in adventitia can enhance the formation of neointima. Non-bone marrow CD34⁺ cells could differentiate into ECs after femoral artery injury, maintaining vascular integrity and preventing the formation of neointima. Resident NG2⁺ progenitor cells can differentiate into VSMCs after aortic injury during aortic aneurysm and dissection.