Introduction: Cell-based therapies for the repair and regeneration of various tissues/organs, using stem cells, offer a paradigm shift that may provide alternative therapeutic solutions for a number of diseases.  Adipose-derived stem cells (ASCs) were indicated to differentiate into a variety of cell lineages including neurons in vitro.  In addition, ASCs were proven to have a positive effect on the wound healing process.  Therefore we have performed an in vivo experimental study to find out the effect of ASCs on primary peripheral nerve repair. 
Materials and Methods:  The ASCs were isolated from inguinal fat pads of Fisher rats.  After three passage in control medium (DMEM, 10% FBS), the cells were labeled with DiI and Hoecht 33342 for tracing.  The sciatic nerves of Fisher rats (n=6) were explored bilaterally and sharp incision was made before the branching into peroneal and tibial nerves.  The nerve was immediately coaptated under operating microscope.  The right side was covered with 1x10⁷ ASCs in fibrin glue, and fibrin glue without ASCs was applied to the left side as a control.  Functional analyses by walking gate analysis and electroneurography (ENG) were performed after 3 and 6 month of nerve coaptation.  Structural evaluation were performed by Hematoxylin and Eosin (HE) staining, immunohistochemical staining with anti-S100 protein and anti-VEGF, and scanning electron microscopy (SEM).  
Results:  Walking gate analysis after 3 months of nerve coaptation revealed that the sciatic function indexes (SFI) were -108.677±7.436 and -83.061±8.183 in the control and experimental group, respectively.  After 6 months, SFI were -83.246±7.352 and -62.256±7.349 in the control and experimental group, respectively.  ENG at 6 months showed that nerve conduction velocity was 34.88±5.15 m/sec in the control and 48.01±6.83 m/sec in the experimental group.  In addition, the conduction percentage of the given voltage was 5.37±1.89% in the control and 9.33±2.01% in the experimental group.  There was a statistically significant difference in all of the evaluation methods (p<0.05).  HE staining and immunohistochemical staining for S-100 revealed that DiI-positive ASCs were existed in both endothelium of the capillary within the epineurium and the peripheral axons.  SEM revealed that more myelinated axons were abundant in the experimental group.  Finally, increase expression of VEGF was found in the experimental group compare to the control group. 
Conclusions:  These findings suggest that ASCs might help in the primary healing process of the peripheral nerve injury directly and indirectly.  Direct effect is mainly the differentiation of ASCs into both endothelial cells and Schwann cells.  Indirect effect may be involved in the increase expression of angiogenic growth factors such as VEGF.