Use of Induced Neural Precursor Cells From Adipose-Derived Stem Cells With Chitosan Conduit to Repair Peripheral Nerve Injury

Purpose:

To explore the in vivo therapeutic effect of chitosan conduit containing with induced neural progenitor cells (NPC) from adipose-derived stem cells (ASC) by using model of sciatic nerve transection in adult rat.

Materials and Methods:

The human ASC from healthy donors are obtained with informed consent and approved according to the procedures of the institutional review board. P3 ASCs are seeded onto chitosan coated surface to form free floating neurospheres spontaneously after 2 days¹. We use 200~250 g S-D rat to develop the model of sciatic nerve transection with 1-cm critical nerve gap, which are randomly assigned to five groups: Group1-sham operation(Sham); Group2-silicon neural tube(S); Group3-silicon neural tube seeded with chitosan(C); Group4-silicon tube plus induced NPCs(S+N); Group5-chitosan tube plus induced NPCs(C+N). The gait analysis is evaluated at 1, 3 and 6 weeks after surgery. The rat is sacrificed at 6 weeks after surgery for evaluation of the regenerated nerve and muscle using immunohistochemic staining.

Results:

Gait analysis was evaluated using automatic computer-assisted walkway system and revealed significant improvement of the gait parameter of step length and stride length in the treatment group. After 6 weeks, the nerve regenerates through the 1-cm nerve gap and yielded re-myelinated nerve within the nerve conduit. The relative muscle weight, average muscle fiber diameter, ratio of fast adapting muscle fibers of gastrocnemius muscle showed statistically increased in the C+N group. In the regenerated nerve, the ratio of re-myelinated axons, NFH- and GFAP- positive cells were also increased in the treatment groups.

Conclusion:

Via the model of sciatic nerve transection, peripheral nerve regeneration can be induced with the aid of chitosan-coated tube and neural precursor cell, which are demonstrated by analysis of gait analysis, regeneration of effector muscle and re-myelinated nerve. These results light up a scope of incorporation of biomaterials and stem cells to facilitate peripheral nerve regeneration.