Versatile subtypes of pericytes and their roles in spinal cord injury repair, bone development and repair

Abstract

Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit (NVU), pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury (SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics.

Fig. 1

Pericytes in SCI. Schematic representation of the localization, morphology, and coverage of common subtypes of pericytes and vascular endothelial cells in normal spinal cord (a) and injured spinal cord (b)

Fig. 2

Schematic model showing pericytes by the expression of pericyte markers of PDGFRβ, CD146, desmin, and NG2 as examples, and their potential differentiation lineages

Fig. 3

Relationships between different types of pericytes and the SCI microenvironment

Fig. 4

Schematic diagram proposing the role of pericytes in angiogenesis and bone repair. a Pericytes, located in the basement membrane of blood vessels, are the cells that surround endothelial cells in the capillary and veins of the body. b Pericytes communicate with endothelial cells through physical contact and paracrine signals, monitoring and stabilizing the maturation of endothelial cells. c Pericytes promote angiogenesis, which has an important role in maintaining intravascular homeostasis. d–k Pericytes are also an important source of stem cells for bone regeneration with osteogenic potential. d Mediating the differentiation of perivascular stem cells (PSCs) into osteoprogenitor cells. e Promoting the migration of osteoprogenitor cells. f Inducing the proliferation of osteoprogenitor cells. g Inducing the differentiation of osteoblasts via paracrine mode. h–k The proposed role of PSCs in bone development and fracture repair (h), bone formation and defect healing (i), osteonecrosis (j), and spinal fusion (k) as discussed in the manuscript