title: Bridging critical nerve defects through an acellular homograft seeded with autologous schwann cells obtained from a regeneration neuroma of the proximal stump.
abstract: Over the last decade, several models have investigated the usefulness of different biologic and/or synthetic matrices as alternatives to conventional nerve grafts. Still, axonal regeneration did not occur over longer (> 3 cm) distances. One problem may be that a growth-promoting environment not only includes physical cues but also a rich spectrum of different growth factors only provided by reactive Schwann cells. In the current study, we investigated whether a hybrid graft consisting of first-generation autologous Schwann cells seeded onto an acellular auto- or homograft can aid regeneration across a critical nerve defect in a rat model. In this paradigm, Schwann cells were not expanded in vitro but harvested from the proximal stump neuroma at the time of reconstruction and seeded into either an acellular homo- or autograft. Regeneration was then quantitated with functional muscle testing, regular histology, histomorphometry, and retrograde tracing techniques 12 weeks after reconstruction. Results showed successful regeneration over the entire distance regardless of whether Schwann cells were transplanted onto auto- or homologous acellular matrix. Schwann cells did populate both grafts; however, only sensory axons persisted through the entire distance. The functional outcome was dismal with no motor and poor sensory recovery. Control group C with homologous matrix only without Schwann cells showed no signs of directed axonal regeneration. Control group D with autologous reverse graft showed excellent recovery, as was expected. The present experiment sought to create a hybrid graft where the proximal stump neuroma is used as a biological resource for autologous Schwann cells that are seeded unto an acellular matrix, thus providing both physical and chemical support to regenerating axons. The results are encouraging in that successful regeneration was observed over the entire distance; however, only sensory axons had enough regenerative potential to also make end-organ contact. For motor axons, further refinements in conduit preparation have to be done.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Vienna, School of Medicine, Vienna, Austria.
authors.forename: Oskar C
authors.initials: OC
authors.lastname: Aszmann
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Korak
authors.forename: Matthias
authors.initials: M
authors.lastname: Luegmair
authors.forename: Manfred
authors.initials: M
authors.lastname: Frey
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation; D004558:Electric Stimulation; D048091:Guided Tissue Regeneration / Q000379:methods; D007150:Immunohistochemistry; D023421:Models, Animal; D009046:Motor Neurons; D018482:Muscle, Skeletal / Q000294:innervation; D009416:Nerve Regeneration; D009463:Neuroma / Q000473:pathology*; D009475:Neurons, Afferent; D010524:Peripheral Nervous System Neoplasms / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology* / Q000601:surgery; D013979:Tibial Nerve; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous