Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

Abstract

Transplantation of neural stem cells (NSCs) is a potential strategy for the treatment of spinal cord transection (SCT). Here we investigated whether transplanted NSCs would improve motor function of rats with SCT and explored the underlying mechanism. First, the rats were divided into sham, SCT, and NSC groups. Rats in the SCT and NSC groups were all subjected to SCT in T10, and were administered with media and NSC transplantation into the lesion site, respectively. Immunohistochemistry was used to label Nestin-, TUNEL-, and NeuN-positive cells and reveal the expression and location of type I insulin-like growth factor receptor (IGF-1 R). Locomotor function of hind limbs was assessed by Basso, Beattie, Bresnahan (BBB) score and inclined plane test. The conduction velocity and amplitude of spinal nerve fibers were measured by electrophysiology and the anatomical changes were measured using magnetic resonance imaging. Moreover, expression of IGF-1 R was determined by real-time polymerase chain reaction and Western blotting. The results showed that NSCs could survive and differentiate into neurons in vitro and in vivo. SCT-induced deficits were reduced by NSC transplantation, including increase in NeuN-positive cells and decrease in apoptotic cells. Moreover, neurophysiological profiles indicated that the latent period was decreased and the peak-to-peak amplitude of spinal nerve fibers conduction was increased in transplanted rats, while morphological measures indicated that fractional anisotropy and the number of nerve fibers in the site of spinal cord injury were increased after NSC transplantation. In addition, mRNA and protein level of IGF-1 R were increased in the rostral segment in the NSC group, especially in neurons. Therefore, we concluded that NSC transplantation promotes motor function improvement of SCT, which might be associated with activated IGF-1 R, especially in the rostral site. All of the above suggests that this approach has potential for clinical treatment of spinal cord injury.

Targeted inhibition of STAT3 in neural stem cells promotes neuronal differentiation and functional recovery in rats with spinal cord injury

“…In the present study, a more significant increase in the BBB scores of rats transplanted with STAT3-RNAi- transfected NSCs was observed, with an ~50% increase in the BBB scores in that group, compared with the scores in the LC group 5 weeks following SCI. This result is superior compared with that reported by previous studies that only transplanted NSC ( 45 , 50 , 51 ). Furthermore, rats transplanted with STAT3-RNAi-transfected NSCs tended to have higher SCEP amplitudes compared with rats in the LC and SCI groups, suggesting that motor and sensory axonal conduction was reinforced following transplantation with STAT3-RNAi- transfected NSCs ( 52 ).…”

AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

“…At molecular level, neurotrophic factors released by NSCs with the ability of promoting regeneration can help restore the function of the damaged spinal cord 49 . In addition, non-neural tissue near the site of SCI can also be repaired 50 . However, studies have found that NSCs often fail to survive and function in SCI 51 .…”

Electrical Stimulation Promotes Stem Cell Neural Differentiation in Tissue Engineering

“…NSCs located in the specific regions of developing and adult human brain are tissue-specific stem cells and can terminally differentiate into all neural lineages, including neurons, astrocytes, and oligodendrocytes [ 11 ]. The application of NSCs is considered a promising therapeutic strategy for treating of central nervous system diseases, including Parkinson's disease, Alzheimer's disease, and spinal cord repair [ 12 – 14 ]. Preclinical researches NSCs derived from fetal tissues, ESCs, and iPSCs showed enhanced recovery after stroke [ 15 – 17 ] and comparable neurological disorders [ 18 , 19 ].…”