Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice

Abstract

The combination of FK506 treatment with cold preservation of nerve allografts resulted in functional and histomorphometric recovery superior to that with either modality alone.

Nerve Allotransplantation as it Pertains to Composite Tissue Transplantation

“…In the course of our investigations, we also discovered that low dose FK-506 in combination with other immunosuppressive regimes (anti-CD-40 ligand/co-stimulatory blockade and cold preservation in University of Wisconsin solution) continued to enhance peripheral nerve regeneration [5,21]. In contrast, immunosuppressive doses of FK-506 with therapeutic doses of anti-CD-40 ligand/costimulatory blockade abrogates the beneficial effects of FK-506 on nerve regeneration [5].…”

Olfactory Mucosa Mesenchymal Stem Cells and Biomaterials: A New Combination to Regenerative Therapies after Peripheral Nerve Injury

“…Autologous nerve grafts are most indicated since they have all the microstructural components that facilitate axonal migration and have no antigenic components, but the collection of nerves with adequate diameter and the consequences of sacriicing a healthy nerve are important limitations [42]. Allografts, generally from cadaveric donors, despite providing the necessary cellular structures, require immunosuppressive treatments for long periods of time in order to prevent rejections in the receptor [43]. The allografts can be enzymatically processed to become acellular, thus alleviating the need for immunosuppression, presenting high success rates compared to other techniques.…”

The effects of cold preservation and subimmunosuppressive doses of FK506 on axonal regeneration in murine peripheral nerve isografts

“…Such agents include insulin-like growth factor (2-4), prosaposin (5,6), ciliary neurotrophic factor (7,8), acidic fibroblast growth factor (9), hyaluronic acid (10), leupeptin (11) and ganglioside GM1 (12). The immunosuppressive agent FK506, a neuro-immunophilin-binding ligand, has consistently demonstrated significant neuroregenerative properties both in vivo (13)(14)(15)(16)(17)18) and in vitro (19)(20)(21)(22), while the neuroregenerative properties of other neuroimmunophilin-binding ligands such as GPI-1046, L-685,818, V-10,367 and rapamycin are less conclusive (21)(22)(23)(24)(25)(26)(27).…”

“…These investigators have suggested that the release of MAG is dependent on the duration of nerve segment predegeneration and the presence of myelin debris. Indeed, cold preservation of nerve grafts ensures a finite period of nerve graft predegeneration (30,31), and both FK506 and cold preservation significantly decrease myelin debris (15,16).…”