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Validation of a novel animal model for sciatic nerve repair with an adipose-derived stem cell loaded fibrin conduit

Neural Regeneration Research 2018年第5期13卷 854-861页

作者： Maximilian M.Saller Rosa-Eva Huettl Julius M.Mayer Annette Feuchtinger Christian Krug Thomas Holzbach Elias Volkmer Experimental Surgery and Regenerative Medicine (ExperiMed) Department of General Trauma and Reconstructive SurgeryLudwig-Maximilians-University (LMU) Max-Planck-Institute of Psychiatry Department of Stress Neurobiology and Neurogenetics Department of Hand- Plastic-and Aesthetic Surgery Ludwig-Maximilians-University (LMU) Research Unit Analytical Pathology Munich Helmholtz Zentrum Muenchen-German Research Center for Environmental Health (GmbH) Department of Hand and Plastic Surgery Spital Thurgau AG

Despite the regenerative capabilities of peripheral nerves, severe injuries or neuronal trauma of critical size impose immense hurdles for proper restoration of neuro-muscular circuitry. Autologous nerve grafts improve re-establishment of connectivity, but also comprise substantial donor site morbidity. We developed a rat model which allows the testing of different cell applications, i.e., mesenchymal stem cells, to improve nerve regeneration in vivo. To mimic inaccurate alignment of autologous nerve grafts with the injured nerve, a 20 mm portion of the sciatic nerve was excised, and sutured back in place in reversed direction. To validate the feasibility of our novel model, a fibrin gel conduit containing autologous undifferentiated adipose-derived stem cells was applied around the coaptation sites and compared to autologous nerve grafts. After evaluating sciatic nerve function for 16 weeks postoperatively, animals were sacrificed, and gastrocnemius muscle weight was determined along with morphological parameters（g-ratio, axon density ＆ diameter） of regenerating axons. Interestingly, the addition of undifferentiated adipose-derived stem cells resulted in a significantly improved re-myelination, axon ingrowth and functional outcome, when compared to animals without a cell seeded conduit. The presented model thus displays several intriguing features： it imitates a certain mismatch in size, distribution and orientation of axons within the nerve coaptation site. The fibrin conduit itself allows for an easy application of cells and, as a true critical-size defect model, any observed improvement relates directly to the performed intervention. Since fibrin and adipose-derived stem cells have been approved for human applications, the technique can theoretically be performed on humans. Thus, we suggest that the model is a powerful tool to investigate cell mediated assistance of peripheral nerve regeneration.

关键词： critical-size nerve defect fibrin conduit autologous nerve transplant peripheral nerve regeneration adipose-derived stem/progenitor cells sciatic function index sciatic nerve re-innervation axon guidance peripheral circuitry

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