Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration.
Current treatments of injured peripheral nerves often fail to mediate satisfactory functional recovery. For axonal regeneration, neurotrophic factors (NTFs) play a crucial role. Multiple NTFs and other growth-promoting factors are secreted, amongst others, by Schwann cells (SCs), which also provide cellular guidance for regenerating axons. Therefore, delivery of NTFs and transplantation of autologous or genetically modified SCs with therapeutic protein expression have been proposed. This article reviews polymer-based and cellular approaches for NTF delivery, with a focus on SCs and strategies to modulate SC gene expression. Polymer-based NTF delivery has mostly resided on nerve conduits (NC). While NC have generally provided prolonged NTF release, their therapeutic effect has remained significantly below that achieved with autologous nerve grafts. Several studies demonstrated enhanced nerve regeneration using NC seeded with SCs. The SCs have sometimes been modified genetically using non-viral or viral vectors. Whereas non-viral vectors produced poor transgene delivery, adenoviral vectors mediated high transgene transduction efficiency of SCs. Further improvements of safety and transgene expression of adenoviral vector may lead to rapid translation of pre-clinical research to clinical trials.
Madduri
Srinivas
S
Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Gander
Bruno
B
D000818:Animals; D017690:Cell Transplantation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D009414:Nerve Growth Factors / Q000235:genetics*; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism*; D014780:Viruses / Q000235:genetics
D009414:Nerve Growth Factors