Mesenchymal Stem Cells and Inflammatory Cardiomyopathy: Cardiac Homing and Beyond
Figure 1
Proposed pathways how inflammation induces cardiac homing of mesenchymal stem cells. (a) TNF-α and/or Coxsackievirus B3 (CVB3) trigger the induction of cardiac expression of monocyte chemoattractant protein-1 (MCP-1) also known as CCL2. At the same time, the expression of the corresponding chemokine receptor CCR2 is induced on mesenchymal stem cells (MSCs), stimulating cardiac migration. (b) TNF-α induces vascular cellular adhesion molecule- (VCAM-)1 expression on the cardiac endothelium. The VLA-4/VCAM-1 axis is important for firm MSC adherence to endothelial cells. Next, MSCs transmigrate through the endothelium which also requires the interaction of VCAM-1 and VLA-4. Finally, MSCs invade through the basement membrane and the extracellular matrix (ECM) via their secretion of matrix metalloproteinase- (MMP-)2, MMP-9, and membrane type 1 MMP (MT1-MMP), which are upregulated by TNF-α. In the heart, MSCs can exert cardioprotective effects, including their anti-inflammatory, antifibrotic, and antiapoptotic features, among others, via interleukin- (IL-)10 and nitric oxide (NO).
