A Pericyte Origin of Spinal Cord Scar Tissue

Abstract

There is limited regeneration of lost tissue after central nervous system injury, and the lesion is sealed with a scar. The role of the scar, which often is referred to as the glial scar because of its abundance of astrocytes, is complex and has been discussed for more than a century. Here we show that a specific pericyte subtype gives rise to scar-forming stromal cells, which outnumber astrocytes, in the injured spinal cord. Blocking the generation of progeny by this pericyte subtype results in failure to seal the injured tissue. The formation of connective tissue is common to many injuries and pathologies, and here we demonstrate a cellular origin of fibrosis.

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification

“…Additionally, a recent study by Kan et al (2013) identified that cells presenting the glutamate transporter GLAST were found to contribute to the formation of ectopic bone, and that these GLAST + cells appeared to be distinct from the Tie2 + population identified by Woscyzna et al (2012) [94]. Pericyte populations have been shown to express GLAST [99], and consequently this information further highlighted the potential role of these cells during HO. However, due to a lack of novel surface markers that can be used for the definitive phenotypic characterisation of pericytes in vivo, the role of these cells in HO remains elusive.…”

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

“…The PDGFRb þ CD105 þ cells observed in the ischemic brain tissue are likely stromal cells derived from 'type A' PCs, which have recently been reported to proliferate and seal the tissue defect after surgical lesion of the spinal cord. 17 The authors of this important study were able to track the origin of PDGFRb þ cells to mural cells, which express both PDGFRb and CD13.…”

“…Our results suggest that, far from being a mere collection of debris, the ischemic CNS tissue exhibits a surprisingly high degree of remodeling in rodents and humans. Although scarring may seal the injured tissue after dorsal funiculus incision or dorsal hemisection of the spinal cord in mice, 17 the generation of excessive ECM may also negatively affect the structure and function of organs. 27 In the injured CNS, fibroblast-like stromal cells may impede axonal outgrowth by expressing semaphorin3.…”

“…These cells proliferate extensively into fibroblast-like cells that generate fibrous extracellular matrix (ECM) after spinal cord injury. 17 We hypothesized that cerebral ischemia results in the degeneration of brain microvascular PCs, and induces the proliferation of vascular stromal cells which contribute to tissue remodeling. Using (1) a model of experimental stroke in wild-type and transgenic mice expressing GFP under the control of the PC/ mural cell-specific rgs5 promoter, 18 (2) bone marrow (BM) chimeric mice, and (3) a comprehensive collection of human stroke samples, we show that cerebral ischemia decimates the population of capillary PCs in the brain while inducing the proliferation of a novel population of vessel wall-derived PDGFRb þ stromal cells.…”

Amyloid‐beta 1‐40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro

“…It may thus be that the decreased activity of caspase 3/7 in response to monomer Aβ1‐40 seen in our study contributes to both the increased cell viability and the increased cell division. Finally, it is important to point out that cell cultures can never replicate a biological system and although pericyte proliferation does occur in the human brain (Fernandez‐Klett et al., 2013; Goritz et al., 2011; Matsushita et al., 2015; Paul et al., 2012), the conditions and rate in the brain are not comparable to the same in a Petri dish. Hence, we would like to stress that our cell model is useful foremost as a tool to demonstrate that differences in pericyte response to Aβ depend on both aggregation form and specie.…”