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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 被引量:15

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
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摘要 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 X2 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) IJV vs. (428.84±193.01) IJV 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. 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 X2 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) IJV vs. (428.84±193.01) IJV 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.
出处 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第5期909-917,共9页 中华医学杂志(英文版)
基金 This work was supported by the grant from the International Cooperation Research Foundation of National Natural Science Foundation of China (No. 30540450581). Conflict of interest: none.
关键词 spinal cord injury tissue engineering neural stem cells Schwann cells poly(L-lactic-co-glycolic acid) scaffold spinal cord injury tissue engineering neural stem cells Schwann cells poly(L-lactic-co-glycolic acid) scaffold
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