Schwann cell grafts support axonal growth following spinal cord injury, but a boundary forms between the implanted cells and host astrocytes. Axons are reluctant to exit the graft tissue in large part due to the surrounding inhibitory environment containing chondroitin sulphate proteoglycans (CSPGs). We use a lentiviral chondroitinase ABC, capable of being secreted from mammalian cells (mChABC), to examine the repercussions of CSPG digestion upon Schwann cell behaviour in vitro. We show that mChABC transduced Schwann cells robustly secrete substantial quantities of the enzyme causing large-scale CSPG digestion, facilitating the migration and adhesion of Schwann cells on inhibitory aggrecan and astrocytic substrates. Importantly, we show that secretion of the engineered enzyme can aid the intermingling of cells at the Schwann cell-astrocyte boundary, enabling growth of neurites over the putative graft/host interface. These data were echoed in vivo. This study demonstrates the profound effect of the enzyme on cellular motility, growth and migration. This provides a cellular mechanism for mChABC induced functional and behavioural recovery shown in in vivo studies. Importantly, we provide in vitro evidence that mChABC gene therapy is equally or more effective at producing these effects as a one-time application of commercially available ChABC.

• MeSH
• astrocyty metabolismus   MeSH
• axony metabolismus   MeSH
• buněčná adheze MeSH
• centrální nervový systém metabolismus   MeSH
• chondroitinasa ABC metabolismus   MeSH
• chondroitinsulfát proteoglykany metabolismus   MeSH
• genetická terapie MeSH
• integriny metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• Lentivirus enzymologie   MeSH
• neurity metabolismus   MeSH
• neuroglie metabolismus   MeSH
• neurony metabolismus   MeSH
• periferní nervový systém metabolismus   MeSH
• pohyb buněk MeSH
• poranění míchy patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• regenerace nervu účinky léků   MeSH
• Schwannovy buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chondroitinasa ABC MeSH
• chondroitinsulfát proteoglykany MeSH
• integriny MeSH