New nerve regeneration strategy combining laminin-coated chitosan conduits and stem cell therapy

• Published in: Acta biomaterialia 2013-05, Vol.9 (5), p.6606-6615
• Main Authors: Hsu, Sung-Hao, Kuo, Wen-Chun, Chen, Yu-Tzu, Yen, Chen-Tung, Chen, Ying-Fang, Chen, Ko-Shao, Huang, Wen-Cheng, Cheng, Henrich
• Format: Article
• Language: English
• Subjects: Animals; bone marrow; cell adhesion; cell death; Chitosan; Chitosan - administration & dosage; Female; in vivo studies; In vivo test; Laminin; Laminin - administration & dosage; Male; motor neurons; muscles; Nerve Regeneration; nerve tissue; PC12 Cells; peroxidase; Rats; Rats, Sprague-Dawley; regrowth; spinal cord; Stem cell; Stem Cell Transplantation; stem cells; surgery; Tissue Engineering
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2013.01.025

Nerve regeneration remains a difficult challenge due to the lack of safe and efficient matrix support. We designed a laminin (LN)-modified chitosan multi-walled nerve conduit combined with bone marrow stem cell (BMSC) grating to bridge a 10mm long gap in the sciatic nerve of Sprague–Dawley rats. The repair outcome was monitored during 16weeks after surgery. Successful grafting of LN onto the chitosan film, confirmed by immunolocalization, significantly improved cell adhesion. In vivo study showed that newly formed nerve cells covered the interior of the conduit to connect the nerve gap successfully in all groups. The rats implanted with the conduit combined with BMSCs showed the best results, in terms of nerve regrowth, muscle mass of gastrocnemius, function recovery and tract tracing. Neuroanatomical horseradish peroxidase tracer analysis of motor neurons in the lumbar spinal cord indicated that the amount and signal intensity were significantly improved. Furthermore, BMSCs suppressed neuronal cell death and promoted regeneration by suppressing the inflammatory and fibrotic response induced by chitosan after long-term implantation. In summary, this study suggests that LN-modified chitosan multi-walled nerve conduit combined with BMSCs is an efficient and safe conduit matrix for nerve regeneration.