Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury

Abstract

Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1␣1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1␣1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1␣1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation.

Imaging Cleared Intact Biological Systems at a Cellular Level by 3DISCO

“…In addition, several publications by independent research groups already used this method to obtain imaging results 22,23 . Nevertheless, different tissue clearing procedures could be advantageous for different conditions.…”

Cell biology of spinal cord injury and repair

“…Pericytes and fibroblast-lineage cells are major components of non-neural lesion core ( Figure 1A, Figure 3A, and refs. 8,9). Molecules produced by these cells have axon-inhibitory properties in vitro, including certain collagens and chondroitin sulfate proteoglycans (CSPGs) (75).…”

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat

“…This stromal scar is mainly the result of collagen production by fibroblasts and pericytes, which forms a physical barrier and serves as a framework for the deposition of axon growth inhibitory molecules such as semaphorin-3A (Sema3A), tenascin-C, and the CSPGs phosphocan and neuron-glial antigen 2 (NG2). [18][19][20][21] Release of profibrotic cytokines, such as transforming growth factor-b1 and -b2 (TGF-b1 and TGF-b2), by microglia and infiltrating macrophages is thought to drive this scarring process. [22][23] Tissue engineering represents a promising approach for modulating the inhibitory environment of the SCI lesion site to facilitate recovery.…”

“…[49][50][51][52][53] Interactions with the protein-coated biomaterial can induce a phenotypic switch in the macrophages to an M2-like state, in which they secrete anti-inflammatory cytokines such as interleukin-10 (IL-10). [21][22][23] Macrophage activation and adhesion has been shown to be more robust with hydrophilic polymers that are charged rather than uncharged, with the activated macrophages showing an anti-inflammatory cytokine profile. 54 Therefore, the presence of an implanted OPF+ polymer scaffold could dramatically change the pattern of lesion development after SCI.…”