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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

The survival of injured host neurons in L1 Clarke’s nucleus (CN) and L3 ventral horn of spinal cord at 8 weeks after cell transplantation. a–c Neural red staining of L1 CN in the gelatin sponge (GS) (a), mesenchymal stem cells (MSCs) (b), and NT-3-MSCs (MN) + TrkC-MSCs (MT) (c) groups. Arrows indicate the survival neurons in CN. d–f Neural red staining of L3 ventral horn in the GS (d), MSCs (e), and MN + MT (f) groups. Arrowheads indicate the survival neurons in ventral horn. g, h Bar charts show the number of survival neurons in CN and ventral horn. In the MN + MT group, the number of survival neurons in CN was more than in the MSCs and GS groups (g) (*P < 0.05, #P < 0.05). The number of survival neurons in ventral horn was more in the MSCs and MN + MT groups compared with the GS group (h) (*P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the number of survival neurons. Scale bars = 50 μm
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Fig6: The survival of injured host neurons in L1 Clarke’s nucleus (CN) and L3 ventral horn of spinal cord at 8 weeks after cell transplantation. a–c Neural red staining of L1 CN in the gelatin sponge (GS) (a), mesenchymal stem cells (MSCs) (b), and NT-3-MSCs (MN) + TrkC-MSCs (MT) (c) groups. Arrows indicate the survival neurons in CN. d–f Neural red staining of L3 ventral horn in the GS (d), MSCs (e), and MN + MT (f) groups. Arrowheads indicate the survival neurons in ventral horn. g, h Bar charts show the number of survival neurons in CN and ventral horn. In the MN + MT group, the number of survival neurons in CN was more than in the MSCs and GS groups (g) (*P < 0.05, #P < 0.05). The number of survival neurons in ventral horn was more in the MSCs and MN + MT groups compared with the GS group (h) (*P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the number of survival neurons. Scale bars = 50 μm

Mentions: To determine neuroprotection of the grafts in spinal cord transection, the survival of axotomized neurons in CN (L1 segment) and injured motor neurons (by transneuronal anterograde degeneration) in ventral horn (L3 segment) was evaluated with the neutral red staining (Fig. 6a–g). In the MN + MT group, the number of surviving CN neurons was more than in the GS and MSC groups (Fig. 6g; P < 0.05). In contrast to GS transplantation, MSC transplantation regimen also effectively rescued some of the axotomized host neurons (Fig. 6g). Furthermore, the number of survival of motor neurons in the MN + MT and MSC groups was significantly more than in the GS group (Fig. 6h). Overall, MN + MT transplantation treatment resulted in the highest number of surviving neurons axotomized (Fig. 6g; P < 0.05).Fig. 6


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)

The survival of injured host neurons in L1 Clarke’s nucleus (CN) and L3 ventral horn of spinal cord at 8 weeks after cell transplantation. a–c Neural red staining of L1 CN in the gelatin sponge (GS) (a), mesenchymal stem cells (MSCs) (b), and NT-3-MSCs (MN) + TrkC-MSCs (MT) (c) groups. Arrows indicate the survival neurons in CN. d–f Neural red staining of L3 ventral horn in the GS (d), MSCs (e), and MN + MT (f) groups. Arrowheads indicate the survival neurons in ventral horn. g, h Bar charts show the number of survival neurons in CN and ventral horn. In the MN + MT group, the number of survival neurons in CN was more than in the MSCs and GS groups (g) (*P < 0.05, #P < 0.05). The number of survival neurons in ventral horn was more in the MSCs and MN + MT groups compared with the GS group (h) (*P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the number of survival neurons. Scale bars = 50 μm
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig6: The survival of injured host neurons in L1 Clarke’s nucleus (CN) and L3 ventral horn of spinal cord at 8 weeks after cell transplantation. a–c Neural red staining of L1 CN in the gelatin sponge (GS) (a), mesenchymal stem cells (MSCs) (b), and NT-3-MSCs (MN) + TrkC-MSCs (MT) (c) groups. Arrows indicate the survival neurons in CN. d–f Neural red staining of L3 ventral horn in the GS (d), MSCs (e), and MN + MT (f) groups. Arrowheads indicate the survival neurons in ventral horn. g, h Bar charts show the number of survival neurons in CN and ventral horn. In the MN + MT group, the number of survival neurons in CN was more than in the MSCs and GS groups (g) (*P < 0.05, #P < 0.05). The number of survival neurons in ventral horn was more in the MSCs and MN + MT groups compared with the GS group (h) (*P < 0.05). One-way analysis of variance with least significant difference test statistics was performed to compare the number of survival neurons. Scale bars = 50 μm
Mentions: To determine neuroprotection of the grafts in spinal cord transection, the survival of axotomized neurons in CN (L1 segment) and injured motor neurons (by transneuronal anterograde degeneration) in ventral horn (L3 segment) was evaluated with the neutral red staining (Fig. 6a–g). In the MN + MT group, the number of surviving CN neurons was more than in the GS and MSC groups (Fig. 6g; P < 0.05). In contrast to GS transplantation, MSC transplantation regimen also effectively rescued some of the axotomized host neurons (Fig. 6g). Furthermore, the number of survival of motor neurons in the MN + MT and MSC groups was significantly more than in the GS group (Fig. 6h). Overall, MN + MT transplantation treatment resulted in the highest number of surviving neurons axotomized (Fig. 6g; P < 0.05).Fig. 6

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