title: Transplantation of artificial neural construct partly improved spinal tissue repair and functional recovery in rats with spinal cord transection.
abstract: Delivery of cellular and/or trophic factors to the site of injury may promote neural repair or axonal regeneration and return of function after spinal cord injury. Engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic molecules. To explore therapeutic potential of engineered neural tissue, we generated an artificial neural construct in vitro, and transplanted this construct into a completely transected spinal cord of adult rats. Two months later, behavioral analysis showed that the locomotion recovery was significantly improved compared with control animals. Immunoreactivity against microtubule associated protein 2 (Map2) and postsynaptic density 95 (PSD95) demonstrated that grafted cells had a higher survival rate and were able to differentiate toward neuronal phenotype with ability to form synapse-like structure at the injury site; this was also observed under the electron microscope. Immunostaining of neurofilament-200 (NF-200) showed that the number of nerve fibers regrowing into the injury site in full treatment group was much higher than that seen in other groups. Furthermore, Nissl staining revealed that host neuron survival rate was significantly increased in rats with full treatments. However, there were no biotin dextran amine (BDA) anterograde tracing fibers crossing through the injury site, suggesting the limited ability of corticospinal tract axonal regeneration. Taken together, although our artificial neural construct permits grafted cells to differentiate into neuronal phenotype, synaptogenesis, axonal regeneration and partial locomotor function recovery, the limited capacity for corticospinal tract axonal regeneration may affect its potential therapy in spinal cord injury.
authors.affiliation: Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bao-Ling
authors.initials: BL
authors.lastname: Du
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Zeng
authors.forename: Liu-Min
authors.initials: LM
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Da-Ping
authors.initials: DP
authors.lastname: Quan
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001710:Biotin / Q000031:analogs & derivatives; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003911:Dextrans; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000627:therapeutic use*; D008124:Locomotion / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D058953:Neural Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000627:therapeutic use*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D014162:Transfection / Q000379:methods; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D003911:Dextrans; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C076397:biotinylated dextran amine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001710:Biotin