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The effects of scar resection in chronic complete spinal cord injury(SCI) and the effects of scar resection combined with decellularized hydrogel (scaffold)

ABSTRACT: This study examines the molecular effects of surgical scar resection in　complete chronic spinal cord injury (SCI) through RNA sequencing. Results show that scar resection alters gene expression, with downregulation of axonal growth inhibitors and upregulation of neuroprotective genes. Additionally, the application of a decellularized extracellular matrix (dECM) hydrogel as a scaffold promoted angiogenesis. Gene Ontology analysis indicated enrichment of immune-related processes, suggesting that scar resection improves the spinal cord microenvironment for neural repair. These findings indicate the potential of combining scar resection with scaffolding to support recovery after chronic complete SCI.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE278491 | GEO | 2024/10/08

REPOSITORIES: GEO

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Project description:The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.

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The effects of scar resection in chronic complete spinal cord injury(SCI) and the effects of scar resection combined with decellularized hydrogel (scaffold)

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