title: Co-transplantation of neural stem cells and Schwann cells within poly (L-lactic-co-glycolic acid) scaffolds facilitates axonal regeneration in hemisected rat spinal cord.
abstract: BACKGROUND
  Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells (NSCs) could survive in poly(L-lactic-co-glycolic acid) (PLGA) scaffolds and, when cografted with Schwann cells (SCs), could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function.
  
  
  METHODS
  NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student's t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance (ANOVA) was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials (CMEPs) and Basso, Beattie & Bresnahan locomotor rating scale (BBB) score. The χ(2) test was used to determine the differences in recovery percentage of CMEPs.
  
  
  RESULTS
  NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs ((1.7831 ± 0.0402)% vs. (1.4911 ± 0.0313)%, P < 0.001). Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA + NSCs + SCs group was more than that in PLGA + NSCs group and in PLGA group ((110.25 ± 30.46) vs. (18.25 ± 3.30) and (11.25 ± 5.54), P < 0.01). The percentage of CMEPs recovery in PLGA + NSCs + SCs group was higher than in the other groups (84.8% vs. 50.0% and 37.5%, P < 0.05). The amplitude of CMEPs in PLGA + NSCs + SCs group was higher than in the other groups ((1452.63 ± 331.70) µV vs. (428.84 ± 193.01) µV and (117.33 ± 14.40) µV, P < 0.05). Ipsilateral retransection resulted in disappearance again and functional loss of CMEPs for a few days. But contralateral retransection completely damaged the bilateral motor function.
  
  
  CONCLUSIONS
  NSCs can survive in PLGA scaffolds, and SCs promote NSCs to survive and differentiate towards neurons in vivo which even might form synaptic connection. The scaffolds seeded with cells facilitate axonal regeneration and myelination and motor function recovery. But regenerating axons have limited contribution to motor function recovery.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.forename: Hong
authors.initials: H
authors.lastname: Wan
authors.forename: Shu-yu
authors.initials: SY
authors.lastname: Hao
authors.forename: De-zhi
authors.initials: DZ
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Chuan-chuan
authors.initials: CC
authors.lastname: Gao
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Shen-guo
authors.initials: SG
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D005455:Fluorescent Antibody Technique; D019344:Lactic Acid / Q000737:chemistry*; D009416:Nerve Regeneration / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000628:therapy*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid