Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

Abstract

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

Keywords: Heart; MSC; Mesenchymal stem cell; Muscle; PSC; Perivascular stem cell.

Fig. 1

Immunohistochemistry demonstrating the intimate relationship of pericytes to endothelial cells. (A) Adult mouse skeletal muscle pericytes expressing CD146 and PDGFRβ surround CD31⁺ microvascular endothelial cells. (B) Adult human skeletal muscle pericytes co-expressing CD90 and CD146 surround CD146+ microvascular ECs.

Fig. 2

Skeletal muscle pericytes in health and disease. Schematic outlining proposed functions/roles of pericytes in skeletal muscle homeostasis, in the physiological response to injury, and in pathology/disease states.

Fig. 3

Role of the cardiac pericytes in cardiac physiology and disease. (A) Cardiac pericytes as agents of cardiac cell therapy. When injected into the infarcted heart, they enhance angiogenesis and exert other beneficial effects by paracrine mechanisms. (B) Pericytes contribute directly to cardiac fibrosis after cardiac injury by adopting fibroblast fates. They regulate microvascular stability and potentially contribute to “no reflow” after ischemia–reperfusion injury.

Fig. 4

Purified human pericytes and HUVECs co-form a dual-layered microvascular tube in 3D Matrigel plugs. Confocal microscopy revealed the formation of a dual-layer microvascular structure by fluorescent activated cell sorting-purified human pericytes (green) and HUVECs (red) in a 3D Matrigel plug where HUVECs formed an endothelial tube tightly surrounded by pericytes at 72 h after encapsulation: (A) HUVECs, (B) human pericytes, and (C) merge (scale bars: 50 μm).