A research team from several Chinese medical institutions reported on Jun. 24 that modulating specific scar-forming fibroblast subpopulations could promote spinal cord regeneration following injury. The study, published in Burns & Trauma on March 12, describes how targeting CD36-enriched fibroblasts may help reshape the repair environment after spinal cord injury (SCI).
After SCI, a complex lesion microenvironment forms involving astrocytes, fibroblasts, immune cells, blood vessels, and extracellular matrix components. While early scar formation can limit inflammation and preserve structural stability, ongoing fibroblast activation and extracellular matrix deposition create barriers to regeneration. Current clinical approaches focus mainly on reducing secondary damage rather than altering the scar itself.
The researchers used single-cell RNA sequencing and spatial transcriptomic profiling to map CD36 expression in mouse models of SCI. They found that CD36 was concentrated in lesion scars and increased in certain fibroblast subclusters linked to fibrosis progression. Using salvianolic acid B (a CD36 inhibitor) and T5224 (an activator protein-1/c-Jun inhibitor), they observed reduced accumulation of fibrotic fibroblasts, enhanced angiogenesis marked by CD31 expression, improved axonal regrowth, and better hindlimb functional recovery.
Mechanistic studies showed that c-Jun activates Irf8, which then promotes CD36 transcription—establishing a c-Jun-Irf8-CD36 signaling cascade supported by CUT&Tag and dual-luciferase reporter assays. Multi-omic analyses indicated that T5224 selectively restrained abnormal expansion of CD36-positive fibroblast subclusters while shifting their state toward a more repair-permissive phenotype.
The authors said these findings suggest “a more precise way to think about spinal cord scars.” Rather than removing all scar tissue, they said the goal may be “to tune the scar at the right stage—preserving its early protective role while preventing fibroblasts from building a long-lasting fibrotic wall.” They added that identifying c-Jun, Irf8, and CD36 as connected control points offers clearer routes for developing therapies aimed at reshaping the injury microenvironment.
According to the authors, further validation in larger animal models will be needed before translation into human therapy. The work provides groundwork for future strategies using localized drug delivery or combination therapies targeting pathogenic fibroblast subtypes during early stages after SCI.
