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Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.

Qiu XC, Jin H, Zhang RY, Ding Y, Zeng X, Lai BQ, Ling EA, Wu JL, Zeng YS - Stem Cell Res Ther (2015)

Bottom Line: In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons.In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. qiuxuecheng1990@163.com.

ABSTRACT

Introduction: Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy. However, the low neural differentiation frequency of MSCs has limited its application. The present study attempted to explore whether the grafted MSC-derived neural-like cells in a gelatin sponge (GS) scaffold could maintain neural features or transdifferentiate into myelin-forming cells in the transected spinal cord.

Methods: We constructed an engineered tissue by co-seeding of MSCs with genetically enhanced expression of neurotrophin-3 (NT-3) and its high-affinity receptor tropomyosin receptor kinase C (TrkC) separately into a three-dimensional GS scaffold to promote the MSCs differentiating into neural-like cells and transplanted it into the gap of a completely transected rat spinal cord. The rats received extensive post-operation care, including cyclosporin A administrated once daily for 2 months.

Results: MSCs modified genetically could differentiate into neural-like cells in the MN + MT (NT-3-MSCs + TrKC-MSCs) group 14 days after culture in the GS scaffold. However, after the MSC-derived neural-like cells were transplanted into the injury site of spinal cord, some of them appeared to lose the neural phenotypes and instead transdifferentiated into myelin-forming cells at 8 weeks. In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons. And the injured host neurons were rescued, and axon regeneration was induced by grafted MSCs modified genetically. In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.

Conclusion: Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.

No MeSH data available.


Related in: MedlinePlus

Outcomes of electrophysiology, myelin basic protein (MBP) protein level, and behavior at 8 weeks after cell transplantation. a Motor evoked potentials (MEPs) were obtained by electrophysiological analysis in the normal, gelatin sponge (GS), mesenchymal stem cells (MSCs), and NT-3-MSCs (MN) + TrkC-MSCs (MT) groups. b,c Bar charts of MEP latency and amplitude showed that shorter latency and higher amplitude of MEPs were exhibited in the MN + MT group compared with the GS (#P < 0.05) and MSCs (&P < 0.05) groups. d MBP expression in the GS, MSCs, and MN + MT groups was detected by Western blotting (WB). e Bar chart showed that the level of MBP expression was higher in the MN + MT group compared with the GS and MSCs groups (*P < 0.05, #P < 0.05). f Comparison of Basso, Beattie, and Bresnahan (BBB) score (mean ± standard deviation) of the handlimb locomotor function in spinal cord transected rats of the GS, MSCs, and MN + MT groups. In the MN + MT group, BBB score was higher than in the GS and MSCs groups (*P < 0.05, #P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the BBB score. g Three representative images of the handlimbs (red arrows) of the GS, MSCs, and MN + MT groups of rats which were climbing the inclined grids
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Fig7: Outcomes of electrophysiology, myelin basic protein (MBP) protein level, and behavior at 8 weeks after cell transplantation. a Motor evoked potentials (MEPs) were obtained by electrophysiological analysis in the normal, gelatin sponge (GS), mesenchymal stem cells (MSCs), and NT-3-MSCs (MN) + TrkC-MSCs (MT) groups. b,c Bar charts of MEP latency and amplitude showed that shorter latency and higher amplitude of MEPs were exhibited in the MN + MT group compared with the GS (#P < 0.05) and MSCs (&P < 0.05) groups. d MBP expression in the GS, MSCs, and MN + MT groups was detected by Western blotting (WB). e Bar chart showed that the level of MBP expression was higher in the MN + MT group compared with the GS and MSCs groups (*P < 0.05, #P < 0.05). f Comparison of Basso, Beattie, and Bresnahan (BBB) score (mean ± standard deviation) of the handlimb locomotor function in spinal cord transected rats of the GS, MSCs, and MN + MT groups. In the MN + MT group, BBB score was higher than in the GS and MSCs groups (*P < 0.05, #P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the BBB score. g Three representative images of the handlimbs (red arrows) of the GS, MSCs, and MN + MT groups of rats which were climbing the inclined grids

Mentions: As indicators of function and behavior recovery, electrophysiological measurement, BBB open-field locomotor rating scale, and grid climbing test were performed at 8 weeks post-transplantation. To confirm whether remyelination and axonal regeneration in the injury/graft site of spinal cord could be related with function recovery, we measured the MEPs in four groups of rats (Fig. 7a). In the normal group, stimulation at SMC evoked a large response amplitude (0.31 ± 0.04 mV) and shortened latency (8.70 ± 1.25 ms) of MEPs (Fig. 7b,c). Notably, in the MN + MT group, the response amplitude (0.16 ± 0.06 mV) and latency (12.55 ± 2.56 ms) of MEPs were significantly more improved (P < 0.05) than in the GS group (amplitude of 0.06 ± 0.02 mV and latency of 19.42 ± 2.95 ms) and the MSC group (amplitude of 0.11 ± 0.02 mV and latency of 20.00 ± 2.51 ms) (Fig. 7b,c). Through WB analysis, the level of MBP expression in the injury/graft site of spinal cord was the highest in the MN + MT group when compared with the GS and MSC groups (Fig. 7d, e; P < 0.05). The results suggest that remyelination in the injury/graft site is increased in the MN + MT group, which may be linked to the nerve conduction improvement.Fig. 7


Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.

Qiu XC, Jin H, Zhang RY, Ding Y, Zeng X, Lai BQ, Ling EA, Wu JL, Zeng YS - Stem Cell Res Ther (2015)

Outcomes of electrophysiology, myelin basic protein (MBP) protein level, and behavior at 8 weeks after cell transplantation. a Motor evoked potentials (MEPs) were obtained by electrophysiological analysis in the normal, gelatin sponge (GS), mesenchymal stem cells (MSCs), and NT-3-MSCs (MN) + TrkC-MSCs (MT) groups. b,c Bar charts of MEP latency and amplitude showed that shorter latency and higher amplitude of MEPs were exhibited in the MN + MT group compared with the GS (#P < 0.05) and MSCs (&P < 0.05) groups. d MBP expression in the GS, MSCs, and MN + MT groups was detected by Western blotting (WB). e Bar chart showed that the level of MBP expression was higher in the MN + MT group compared with the GS and MSCs groups (*P < 0.05, #P < 0.05). f Comparison of Basso, Beattie, and Bresnahan (BBB) score (mean ± standard deviation) of the handlimb locomotor function in spinal cord transected rats of the GS, MSCs, and MN + MT groups. In the MN + MT group, BBB score was higher than in the GS and MSCs groups (*P < 0.05, #P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the BBB score. g Three representative images of the handlimbs (red arrows) of the GS, MSCs, and MN + MT groups of rats which were climbing the inclined grids
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482203&req=5

Fig7: Outcomes of electrophysiology, myelin basic protein (MBP) protein level, and behavior at 8 weeks after cell transplantation. a Motor evoked potentials (MEPs) were obtained by electrophysiological analysis in the normal, gelatin sponge (GS), mesenchymal stem cells (MSCs), and NT-3-MSCs (MN) + TrkC-MSCs (MT) groups. b,c Bar charts of MEP latency and amplitude showed that shorter latency and higher amplitude of MEPs were exhibited in the MN + MT group compared with the GS (#P < 0.05) and MSCs (&P < 0.05) groups. d MBP expression in the GS, MSCs, and MN + MT groups was detected by Western blotting (WB). e Bar chart showed that the level of MBP expression was higher in the MN + MT group compared with the GS and MSCs groups (*P < 0.05, #P < 0.05). f Comparison of Basso, Beattie, and Bresnahan (BBB) score (mean ± standard deviation) of the handlimb locomotor function in spinal cord transected rats of the GS, MSCs, and MN + MT groups. In the MN + MT group, BBB score was higher than in the GS and MSCs groups (*P < 0.05, #P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the BBB score. g Three representative images of the handlimbs (red arrows) of the GS, MSCs, and MN + MT groups of rats which were climbing the inclined grids
Mentions: As indicators of function and behavior recovery, electrophysiological measurement, BBB open-field locomotor rating scale, and grid climbing test were performed at 8 weeks post-transplantation. To confirm whether remyelination and axonal regeneration in the injury/graft site of spinal cord could be related with function recovery, we measured the MEPs in four groups of rats (Fig. 7a). In the normal group, stimulation at SMC evoked a large response amplitude (0.31 ± 0.04 mV) and shortened latency (8.70 ± 1.25 ms) of MEPs (Fig. 7b,c). Notably, in the MN + MT group, the response amplitude (0.16 ± 0.06 mV) and latency (12.55 ± 2.56 ms) of MEPs were significantly more improved (P < 0.05) than in the GS group (amplitude of 0.06 ± 0.02 mV and latency of 19.42 ± 2.95 ms) and the MSC group (amplitude of 0.11 ± 0.02 mV and latency of 20.00 ± 2.51 ms) (Fig. 7b,c). Through WB analysis, the level of MBP expression in the injury/graft site of spinal cord was the highest in the MN + MT group when compared with the GS and MSC groups (Fig. 7d, e; P < 0.05). The results suggest that remyelination in the injury/graft site is increased in the MN + MT group, which may be linked to the nerve conduction improvement.Fig. 7

Bottom Line: In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons.In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China. qiuxuecheng1990@163.com.

ABSTRACT

Introduction: Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy. However, the low neural differentiation frequency of MSCs has limited its application. The present study attempted to explore whether the grafted MSC-derived neural-like cells in a gelatin sponge (GS) scaffold could maintain neural features or transdifferentiate into myelin-forming cells in the transected spinal cord.

Methods: We constructed an engineered tissue by co-seeding of MSCs with genetically enhanced expression of neurotrophin-3 (NT-3) and its high-affinity receptor tropomyosin receptor kinase C (TrkC) separately into a three-dimensional GS scaffold to promote the MSCs differentiating into neural-like cells and transplanted it into the gap of a completely transected rat spinal cord. The rats received extensive post-operation care, including cyclosporin A administrated once daily for 2 months.

Results: MSCs modified genetically could differentiate into neural-like cells in the MN + MT (NT-3-MSCs + TrKC-MSCs) group 14 days after culture in the GS scaffold. However, after the MSC-derived neural-like cells were transplanted into the injury site of spinal cord, some of them appeared to lose the neural phenotypes and instead transdifferentiated into myelin-forming cells at 8 weeks. In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons. And the injured host neurons were rescued, and axon regeneration was induced by grafted MSCs modified genetically. In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.

Conclusion: Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.

No MeSH data available.


Related in: MedlinePlus