Abstract:

BACKGROUND: Muscle-derived stem cells (MDSCs) have been accepted as seeding cells in tissue engineered artificial nerves. Tacrolimus exhibits anti-immunologic rejection and promotes nerve regeneration and recovery. Whether can combine these factors with acellular nerve to form a new bridge that can inhibit immunologic rejection and promote nerve regeneration is uncertain.
OBJECTIVE: Using the freeze-thawing combined optimized acellular nerve hypotonic-chemical detergent to prepare acellular nerveallograft scaffold. To explore the effect of co-application of MDSCs and FK-506 on nerve regeneration and function recovery following acellular nerve allograft implantation.
METHODS: The sciatic nerve derived from SD rats was prepared nerve bridge after acellular disposal. Gel containing FK-506 and MDSCs was injected into acellular nerveallograft scaffold with 100 μL microsyringe to repair defects. A total of 32 SD rats were randomly divided into 4 groups, with 8 animals in each group. A gap of 10 mm of left sciatic nerve was removed. And then the defects were repaired by extracted nerve graft containing FK-506+MDSCs, MDSCs and FK-506, respectively. In the control group, only hyaluronic acid gel was injected. Sciatic nerve function index (SFI) and electrophysiological exam were performed at weeks 8 and 12 after operation. Gross observation, neurohistological and ultrastructure were observed at week 12 after operation. 
RESULTS AND CONCLUSION: Compared with the same time point, the SFI, recovery rate of the motor nerve conduction velocities (MNCV), and myelinated nerve fibers in grafting part and in its distal part in the FK-506+MDSCs group were superior to other groups (P < 0.05). The nerve grafts were in normal size with considerable blood vessels and slightly connected to peripheral tissues. Compared to other groups, the regenerated nerve fiber in the FK-506+MDSCs group was more density with well-arranged order. A great quantity of Schwann cells proliferated in grafting. The density and diameter of myelinated fiber in the middle and distal part of the grafting were all greater than that of MDSCs and FK-506 groups, and there were few connective tissues between microfascicles, which was close to normal level. The co-application of MDSCs and FK-506 enhances peripheral nerve regeneration and functional recovery in acellular nerve allograft graft. Therefore, MDSCs and FK-506 are synergistic factors in peripheral nerve injury repair.