Femke Mathot

Chapter 1 18 and important neurotrophic factors, but retains the ultrastructure of the nerve. Since 2007, only one decellularized nerve allograft has been FDA approved and is currently readily available in daily clinical practice. Although sensory nerve gaps have been successfully repaired with these Avance® Nerve Grafts, reported outcomes of long segment, large diameter and mixed and motor nerve gaps are consistently inferior to that of autografts. 43, 46, 48 Absence of Schwann cells, intrinsic angiogenic trophic factors, neurotrophic factors and extracellular matrix proteins are hypothesized to cause the inferiority of allografts. Conduits Natural conduits like veins have been used to bridge peripheral nerve gaps in the past, but synthetic conduits have gained more scientific and clinical interest over the years. The NeuraGen® Nerve Guide is a collagen type 1 conduit that was FDA approved in 2001. 49 Conduits lack Schwann cells, a guiding ultrastructure and angiogenic and neurotrophic factors. They have only led to satisfactory outcomes in small-caliber sensory nerve gaps up to 3cm. 50, 51 MESENCHYMAL STEM CELLS Schwann cells, the guiding ultrastructure (particularly in conduits), angiogenic and neurotrophic factors are removed in nerve allografts and conduits. Replacing these components is logically suggested as the solution to enhance outcomes of allografts and conduits to a level equal to that of autografts. As described, Schwann cells fulfill a key role in multiple processes during Wallerian degeneration, axon regeneration and stimulus transmission, by producing neurotrophic, angiogenic and extracellular matrix factors and by forming myelin. 32 Therefore Schwann cells are considered as the obvious required supplementation to the listed autograft substitutes. Although Schwann cells did demonstrate potential as nerve regeneration catalysts, they need to be derived from nerve tissue. Thus their use requires the sacrifice of an autologous nerve; exactly what is intended to be prevented when using nerve autograft substitutes. 52, 53 Mesenchymal stem cells (MSCs) are precursor cells used in numeral medical fields due to their trophic characteristics and differentiation capacities. Environmental signals influence MSCs to produce trophic factors or to differentiate into specific cell types, tailored to the surrounding regenerating tissue. 52, 54, 55 The use of these MSCs as a supplementation to the previously described nerve autograft substitutes is a hopeful research topic. 56, 57 Differentiation of MSCs into Schwann cell-like cells prior to implementation in peripheral nerve injuries is also a suggested strategy to replace the missing Schwann cells. Although this concept is supported by several in vitro studies, in vivo outcomes still need to show if this strategy is cost- and time-efficient. 52, 58, 59 Mesenchymal stem cells can be obtained from mesenchymal tissues like dental pulp, bone marrow and adipose tissue. In contradiction to dental pulp and bone marrow, adipose tissue is easily and less invasively accessible. Higher MSC-yields and rapid proliferation in culture are additional benefits of adipose derived MSCs. 60-63