PURPOSE: Due to the limitations of current surgical methods of long nerve defect repair, new therapeutic approaches are needed to enhance nerve regeneration. Nerve allografts offer an unlimited source of epineural conduits, which can be matched to the recipient's injured nerve diameter and length to support nerve regeneration. Mesenchymal stem cells, due to their anti-inflammatory and neuroregenerative properties are considered a promising approach as a supportive therapy for peripheral nerve injuries. Thus, we propose a novel therapeutic approach for enhancement of nerve regeneration – human epineural conduit (hEC) consisting of human epineural sheath (hES) supported with human mesenchymal stem cells (hMSC). The aim of this study was to evaluate the feasibility of hEC on the peripheral nerve repair in the nude rat model.

METHODS: Sciatic nerve defect (20mm) was created in 24 nude rats. Animals were divided into four experimental groups: Group 1: no repair of the defect, Group 2: autograft repair of the defect, Group 3: hESC repair filled with saline, and Group 4: hESC repair supported with 3×6^10 hMSC. Functional tests of toe-spread and a pinprick analysis was performed at 1, 3, 6, 9, 12 weeks after surgery. At 12 weeks, nerve samples were collected for toluidine blue staining and the assessment of GFAP, NGF, S-100, laminin B by immunostaining. Muscle denervation atrophy was evaluated using Gastrocnemius Muscle Index (GMI) measurements.

RESULTS: Macroscopic evaluation of the conduits at 12 weeks demonstrated shape preservation with good vascularization and devoid of tissue adhesions or local signs of inflammation. The greatest sensory and motor recovery following treatment was observed in Group 2, followed by Group 4, Group 3, and Group 1 (pinprick 3.0 vs. 2.33 vs. 2.0 vs. 0.57; toe-spread 1.83 vs. 1.5 vs. 1.0 vs. 0.14, respectively). GMI was highest for Group 2 (0.346) followed by Group 4 (0.285), Group 3 (0.274), and Group 1 (0.172). Toluidine blue and immunofluorescent staining is currently under evaluation.

CONCLUSIONS: This study successfully confirmed the feasibility of the application of hESC allograft for restoration of peripheral nerve injures. hEC is a promising new technology for regeneration of long gap nerve defects which combines the effect of neurotropic properties of hES and immunomodulating properties of hMSC.

CITATION INFORMATION: Siemionow M, Strojny M, Malewski W, Cwykiel J, Cyran M. Human Epineural Allograft Conduits Supported with Mesenchymal Stem Cells Enhance Peripheral Nerve Regeneration: A Preliminary Report. Am J Transplant. 2016;16 (suppl 3).

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