Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit

Abstract

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.

Regeneration of nerve crush injury using adipose‐derived stem cells: A multimodal comparison

“…Previous studies sought to restore sciatic nerve function after injury by using artificial nerve conduits and scaffolds as well as by delivering cells directly at the lesion site . The criticism has been raised that this route of administration induces additional trauma to the injection site as well as that it is difficult to treat multiple or diffuse sites of injury .…”

“…An insulin 30 gauge needle (Sterican; B. Braun, Melsungen, Germany) was used for all injections. The volume and number of rASCs used were based on our previous experiences …”

“…We proceeded to tissue explantation immediately after acquisition of the MRI data, as previously described . In animals with the PKH26‐pretreated cells, a piece of their nerves was snap frozen with Tissue‐Tek O.C.T compound (Sakura Finetek, Alphen aan den Rijn, The Netherlands) in isopentane precooled to −20 °C.…”

Collagen Type I Conduits for the Regeneration of Nerve Defects

“…Although polylactic acid seems to be functionally inferior compared to collagen and caprolactone, the optimal material and cellular compounds for biodegradable conduits are still subject of intensive research [28,30,31,32]. Furthermore, there has been frequent reporting on the use of conduits pre-seeded with Schwann cells, or pre-seeded with stem cells differentiated into Schwann cells [33,34]. However, none of these approaches have been implemented into clinical practice for various reasons.…”

Adipose Derived Tissue Engineered Heart Valve

“…There the feasibility and safety of autologous ADSC transplantation were tested, e.g. in peripheral nerve repair [37], treatment of Crohn´s disease fistulas [38], osteogenesis imperfecta [39], bladder diseases, urethral sphincter dysfunction associated with birth trauma and hormonal deficiency as well as the regeneration of bladder tissues [40]. Further studies substantiated the therapeutic potential of ADSC by transplanting them in a setting of chronic heart failure [41] or Acute Myocardial Infarction (AMI).…”