Promotion of neuronal differentiation of neural progenitor cells by using EGFR antibody functionalized collagen scaffolds for spinal cord injury repair

• Published in: Biomaterials Vol. 34; no. 21; pp. 5107 - 5116
• Main Authors: Li, Xiaoran, Xiao, Zhifeng, Han, Jin, Chen, Lei, Xiao, Hanshan, Ma, Fukai, Hou, Xianglin, Li, Xing, Sun, Jie, Ding, Wenyong, Zhao, Yannan, Chen, Bing, Dai, Jianwu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2013
• Subjects: Advanced Basic Science; Animals; Antibodies - pharmacology; Antibodies, Monoclonal, Humanized - pharmacology; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical materials; Cell Count; Cell Differentiation - drug effects; Cells (biology); Cetuximab; Collagen - pharmacology; Collagen scaffold; Dentistry; Differentiation; EGFR antibody functionalization; Green Fluorescent Proteins - metabolism; Inhibitors; Mice; Myelin; Myelin proteins; Neural progenitor cells; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - transplantation; Neuronal differentiation; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - immunology; Recovery of Function - drug effects; Scaffolds; Spinal cord; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Spinal cord injury repair; Spinal Cord Regeneration - drug effects; Stem Cell Transplantation; Surgical implants; Tissue Scaffolds - chemistry; EGFR antibody functionalization; Neuronal differentiation; Neural progenitor cells; Collagen scaffold; Spinal cord injury repair; Myelin proteins
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.03.062

Abstract The main challenge for neural progenitor cell (NPC)-mediated repair of spinal cord injury (SCI) is lack of favorable environment to direct its differentiation towards neurons rather than glial cells. The myelin associated inhibitors have been demonstrated to promote NPC differentiation into glial lineage. Herein, to inhibit the downstream signaling activated by myelin associated inhibitors, cetuximab, an epidermal growth factor receptor (EGFR) neutralizing antibody, functionalized collagen scaffold has been developed as a vehicle for NPC implantation. It was found that collagen-cetuximab 1 μg scaffolds enhanced neuronal differentiation and inhibited astrocytic differentiation of NPCs exposed to myelin proteins significantly in vitro . To test the therapeutic effect in vivo , NPCs expressing green fluorescent protein (GFP)-embedded scaffolds have been implanted into the 4 mm-long hemisection lesion of rats. We found that the collagen-cetuximab 5 μg scaffolds induced neuronal differentiation and decreased astrocytic differentiation of NPCs, enhanced axon regeneration, and promoted functional recovery markedly. A well-functionalized scaffold was constructed to improve the recovery of SCI, which could promote the neuronal differentiation of neural progenitor cells in vivo.