Glia repair by a sequential enzymatic debridement and cell grafting
Funded in: 2022, 2023, 2024
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Problem: Repopulating fibrotic scars with neural cell transplants
Target: Test new strategies for local enzymatic debridement of chronic fibrotic scars
Goal: Advance understanding of cell transplantation in chronic SCI
Spinal cord injury (SCI) causes permanent disability because the spinal cord tissue that is damaged is not naturally repaired. Instead, dense fibrotic scar tissue forms at the site of damage that affords no neurological function. Medical care advances and new rehabilitation practices have helped individuals who suffer SCI to recover important functions by stimulating the rewiring of parts of the spinal cord that are spared from damage to bypass the injury.
However, in injuries where the spinal cord tissue damage is extensive, rehabilitation alone does not lead to much return of function because the injury is too large and has too much fibrotic scar to bypass. Repopulating fibrotic scars with neural cell transplants is a promising therapy approach to repopulate SCI lesions with neural cells to support regeneration, but the stiff intractable nature of chronic fibrotic scars makes local retention of cell grafts a major surgical challenge.
To address this, in this project the researchers will test new strategies for local enzymatic debridement of chronic SCI fibrotic scars to improve cell transplantation outcomes. The neuroscientists will use specially formulated nano-carriers to deliver the enzyme collagenase to effectively debride chronic SCI fibrotic scars while minimizing damage to adjacent neural tissue. The researchers will then combine effective enzymatic debridement approaches with neural cell transplantations and apply genetic sequencing and microscopy methods to track transplantation outcomes. They anticipate that this project will advance our understanding of cell transplantation in chronic SCI and provide new tools that can be used for further testing of approaches for repopulating SCI lesions with functioning neural tissue.