Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models

We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group 〉 chemically extracted acellular nerve graft ＋ ciliary neurotrophic factor group 〉 chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair

Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripher-al nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration.

Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects:similar outcomes to autologous nerve grafts

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomo- rphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

Morphological features of allogenic nerve segment in rats after subcutaneous embedment

BACKGROUND ： Some studies demonstrate that allogenic peripheral nerve segment embedded subcutaneously significantly reduce the infiltration of lymphocyte and decrease immunological reaction.OBJECTIVE ： To observe the gross shape, optical and electron microscope results of allogenic nerve segment in rats 2 weeks after subcutaneous embedment, and compare with subcutaneous emdedment of autologous nerve segment. DESIGN ： A randomized and controlled experiment.SETTING ： Department of Orthopaedics of Fifth People＇s Hospital of Zhengzhou; Department of Orthopaedics,First Hospital Affiliated to Chongqing Medical University.MATERIALS ： Totally 30 adult healthy Wistar male rats, with body mass of （200±20） g, were enrolled. Ten rats were chosen as the donors of allogenic nerve transplantation. The other 20 rats were randomly divided into 2 groups： allogenic nerve embedment group and autologous nerve embedment group, with 10 rats in each one. JEM-1220 transmission electron microscope （Japan） and Olympus BX50 optical microscope （Japan） were used. METHODS ： This experiment was carried out at the laboratory of Orthopaedic Department, Chongqing Medical University from October 2000 to April 2002. ① Sciatic nerve of donor rats for allogenic nerve transplantation was cut off at 5 mm distant from pelvic strait.15 mm sciatic nerve segment was chosen from lateral part as graft, allogenic nerve embedment group： 15 mm sciatic nerve form the donor rats was embedded in the posterior part of right legs. Autologous nerve embedment group： 15 mm sciatic nerve segment of autologous left side was embedded in the posterior side of right legs. ② Nerve segment embedded subcutaneously was taken out at postoperative 2 weeks and performed gross observation; then 5 samples chosen randomly respectively from 2 groups and given haematoxylin-eosin staining and observation under optical microscope （×400）;The other 5 samples were made into ultrathin sections （0.5μm）and observed under transmission electron microscope（×17 000）. MAIN OUTCOME MEASURES ： Gross shape, optical and electron microscope results of nerve segments of rats between two groups at 2 weeks after subcutaneous embedment. RESULTS ： ① Results of gross observation： Appearance of nerve segment was similar between 2 groups. ② Results of optical observation： medullary sheath denaturation, axonotmesis, vascular engorgement, desmoplasia of adventitia and infiltration of inflammatory cells were all found in both 2 groups. Inflammatory reaction was a little more severe in the allogenic nerve embedment group than in the autologous nerve embedment groups.③Results of electron microscope ： Similar cataplasia and denaturation of medullary sheath and cataplasia of Schwann cell were all found in the 2 groups. CONCLUSION： Some inflammatory reaction occurs after allogenic nerve embedment, but the activity of Schwann cell is similar to that of peripheral nerve after autologous nerve embedment.