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Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats
Authors:S Rochkind  A Shahar  D Fliss  D El-Ani  L Astachov  T Hayon  M Alon  R Zamostiano  O Ayalon  I E Biton  Y Cohen  R Halperin  D Schneider  A Oron  Z Nevo
Institution:(1) Neural & Vascular Reconstruction Labs, Ness Ziona, Israel;(2) Division of Peripheral Nerve Reconstruction, Departments of Neurosurgery and Otolaryngology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Ramat Aviv, Tel-Aviv, Israel;(3) Department of Clinical Biochemistry, The Raymond and Beverly Sackler Faculty of Exact Sciences, School of Chemistry, Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel;(4) Departments of Gynecology, Obstetrics and Orthopedics, Assaf Harofeh Medical Center, Zerifin, Israel
Abstract:This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate–gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.
Keywords:Olfactory mucosa  Spinal cord  Transection  Transplantation
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