ORIGINAL RESEARCH REPORT Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit Elisabeth A. Kappos, 1,2, * Patricia E. Engels, 1,2, * Mathias Tremp, 1,2 Moritz Meyer zu Schwabedissen, 1,2 Pietro di Summa, 3 Arne Fischmann, 4 Stefanie von Felten, 5 Arnaud Scherberich, 6 Dirk J. Schaefer, 1 and Daniel F. Kalbermatten 1,2 Tissue engineering is a popular topic in peripheral nerve repair. Combining a nerve conduit with supporting adipose-derived cells could offer an opportunity to prevent time-consuming Schwann cell culture or the use of an autograft with its donor site morbidity and eventually improve clinical outcome. The aim of this study was to provide a broad overview over promising transplantable cells under equal experimental conditions over a long- term period. A 10-mm gap in the sciatic nerve of female Sprague-Dawley rats (7 groups of 7 animals, 8 weeks old) was bridged through a biodegradable fibrin conduit filled with rat adipose-derived stem cells (rASCs), differentiated rASCs (drASCs), human (h)ASCs from the superficial and deep abdominal layer, human stromal vascular fraction (SVF), or rat Schwann cells, respectively. As a control, we resutured a nerve segment as an autograft. Long-term evaluation was carried out after 12 weeks comprising walking track, morphometric, and MRI analyses. The sciatic functional index was calculated. Cross sections of the nerve, proximal, distal, and in between the two sutures, were analyzed for re-/myelination and axon count. Gastrocnemius muscle weights were compared. MRI proved biodegradation of the conduit. Differentiated rat ASCs performed significantly better than undifferentiated rASCs with less muscle atrophy and superior functional results. Superficial hASCs supported regeneration better than deep hASCs, in line with published in vitro data. The best regeneration potential was achieved by the drASC group when compared with other adipose tissue-derived cells. Considering the ease of procedure from harvesting to transplanting, we conclude that comparison of promising cells for nerve regeneration revealed that particularly differentiated ASCs could be a clinically translatable route toward new methods to enhance peripheral nerve repair. Introduction Background P eripheral nerve injuries are a serious health concern and leave many patients with lifelong disabilities. The importance of research in the field of tissue engineering should be emphasized as a pathway toward improving the clinical outcomes, which still appear unsatisfactory [1]. Primary repair is limited to injuries in which there is little or no defect and in which, thus, a tension-free coaptation is possible. If a peripheral nerve injury is associated with a loss of substance, autologous nerve grafts are usually employed for bridging the gap [2]. Although seen as gold standard, there are remarkable disadvantages that go along with this treatment, that is, donor site loss of function, formation of potential painful neuromas, structural differences between donor and recipient grafts, and the limited graft material [3,4]. Next generation of nerve repair Alternatively, nerve entubulation is often chosen as the method of treatment to act as a physical guide for regenerating nerve sprouts. Several natural and artificial materials, such as collagen, silicone, fibrin, or vein grafts, are used as such 1 Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Basel, Switzerland. 2 Department of Neuropathology, Institute of Pathology, University Hospital of Basel, Basel, Switzerland. 3 Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Lausanne, Lausanne, Switzerland. 4 Division of Neuroradiology, Department of Radiology, University Hospital of Basel, Basel, Switzerland. 5 Clinical Trial Unit, University Hospital of Basel, Basel, Switzerland. 6 Institute for Surgical Research and Hospital Management, University Hospital of Basel, Basel, Switzerland. *These authors contributed equally to this work. STEM CELLS AND DEVELOPMENT Volume 00, Number 00, 2015 Ó Mary Ann Liebert, Inc. DOI: 10.1089/scd.2014.0424 1