Functional and histological improvement of the injured spinal cord following transplantation of Schwann cells transfected with NRG1 gene.
In this study, we implanted Schwann cells (SCs) transfected with Neuregulin 1 (NRG1) gene into rats with hemisection spinal cord injury, determined its effects on the repair of spinal cord injury and investigated the underlying mechanisms. Primary SCs were cultured, purified, and transfected with NRG1 gene. SCs and SCs transfected with NRG1 gene were implanted, respectively, into rats with hemisection spinal cord injury. Behavior, imaging, electrophysiology, and immuno-histological analyses were performed to evaluate the effect of NRG1 gene-transfected SCs on the repair of spinal cord injury. In vitro studies showed that NRG1 protein was highly expressed in SCs transfected with NRG1 gene. In addition, the receptors for NRG1, ErbB2, and ErbB4, were upregulated in a time-dependent manner. NRG1-transfected SCs secreted large amount of NRG1 proteins in vivo, which efficiently promoted the expression of ErbB2 and ErbB4 in the neurons and neuroglia cells. Moreover, the number of NSE- and GFAP-positive cells was increased. After cell transplantation, many transplanted cells survived and migrated to the areas with spinal cord injuries. The injuries were recovered in all the experimental groups, but the most significant recovery was observed in the group of rats implanted with SCs transfected with NRG1 gene. We conclude that NRG1-transfected SCs can significantly increase the effect on the repair of spinal cord injury. This repair effect is achieved via the upregulation of ErbB receptor in the target cells, increased proliferation of glial cells, and protection of neurons from apoptosis.
Zhang
Jifei
J
Department of Histoembryology, Medical College of Mudanjiang, Mudanjiang City, Heilongjiang Province, China.
Zhao
Fusheng
F
Wu
Geng
G
Li
Yuezhen
Y
Jin
Xiudong
X
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D008297:Male; D023421:Models, Animal; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D066247:Receptor, ErbB-4; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014162:Transfection; D016896:Treatment Outcome
D066246:ErbB Receptors; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C490580:Nrg1 protein, rat; C483804:Erbb2 protein, rat; C587691:Erbb4 protein, rat