A nerve repair conduit containing differentiated adipose-derived stem cells within engineered neural tissue can support and guide neuronal growth in vitro and in vivo

摘要

Tissue-engineered cellular bridging devices for surgical implantation into peripheral nerve injury sites could provide an attractive alternative to autografts. A patient’s own adipose tissue can be used as a source of cells that provide the trophic support and pro-regenerative behaviour elicited by Schwann cells in an autograft. Adipose-derived stem cells can be differentiated towards a Schwann cell-like phenotype in vitro (dADSC). Here we report the development of a living replacement tissue using therapeutically relevant cells in an engineered neural tissue (ENT). ENT is made from a cellular collagen gel that is tethered at each end to permit the cells to self-align; this is subjected to a compression process to produce a stable biomaterial. Experiments using cell death assays, immunostaining and confocal microscopy show that dADSCs can be successfully incorporated within ENT - dADSCs survive and maintain their alignment following the stabilisation process to form sheets of an aligned cellular biomaterial (ENT). Primary rat neurons growing on the surface of ENT extended neurites that were guided by the orientation of the aligned dADSCs. These sheets of ENTwere rolled into columns and then packed together within a clinically approved tube, NeuraWrapTM. Testing this ‘engineered endoneurium’ in the rat sciatic nerve model showed that neuronal growth was supported and guided by ENTand demonstrates the potential of the device to offer an alternative to nerve autografts.