Limits...
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

Transdifferentiation of transplanted mesenchymal stem cell (MSC)-derived neural-like cells in the injury/graft site of spinal cord. a Some of the grafted MSCs transdifferentiated into myelin-forming cells (white arrowheads, adenomatous polyposis coli (APC)-positive and myelin basic protein (MBP)-positive) in the NT-3-MSC (MN) + TrkC-MSCs (MT) group, but not in the MSCs group, at 8 weeks after transplantation. b Pie charts show the percentage of APC-positive and MBP-positive cells from grafted MSC-derived neural-like cells. c Grafted MSC-derived neural-like cells lost their affinity for the neuron markers (Tju-1-negative and microtubule-associated protein 2 (Map2)-negative) at 8 weeks after transplantation. At 3 days, the grafted MSC-derived neural-like cells were intensely immunostained with neuron markers (white arrowheads, Tju-1-positive and Map2-positive) and some of them began to express myelin-forming cell maker (white arrowhead, APC-positive). Scale bars = 25 μm. Tju-1, β-tubulin III
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4482203&req=5

Fig3: Transdifferentiation of transplanted mesenchymal stem cell (MSC)-derived neural-like cells in the injury/graft site of spinal cord. a Some of the grafted MSCs transdifferentiated into myelin-forming cells (white arrowheads, adenomatous polyposis coli (APC)-positive and myelin basic protein (MBP)-positive) in the NT-3-MSC (MN) + TrkC-MSCs (MT) group, but not in the MSCs group, at 8 weeks after transplantation. b Pie charts show the percentage of APC-positive and MBP-positive cells from grafted MSC-derived neural-like cells. c Grafted MSC-derived neural-like cells lost their affinity for the neuron markers (Tju-1-negative and microtubule-associated protein 2 (Map2)-negative) at 8 weeks after transplantation. At 3 days, the grafted MSC-derived neural-like cells were intensely immunostained with neuron markers (white arrowheads, Tju-1-positive and Map2-positive) and some of them began to express myelin-forming cell maker (white arrowhead, APC-positive). Scale bars = 25 μm. Tju-1, β-tubulin III

Mentions: At 8 weeks after surgical procedure, survival and distribution of grafted GFP-positive cells in GS scaffold were clearly evident in most of the injury/graft sites of spinal cords. Thus, 53.58 % of grafted GFP-positive cells expressed the mature oligodendrocyte marker APC (Fig. 3a,b), and 31.12 % of the cells expressed the other mature oligodendrocyte marker MBP (Fig. 3a,b) in the injury/graft site in the MN + MT group. On the other hand, APC- and MBP-positive cells were not observed in the MSC group (Fig. 3a). Interestingly, Tju-1- and MAP2-positive cells were not observed in the MSC and MN + MT groups (Fig. 3c). To further explore whether differentiating MSCs could maintain the neural-like cell phenotype in the early period of transplantation, neural markers of the MSCs grafted were examined in the MN + MT group. The results showed that Tju-1-, Map2-, and APC-positive cells were observed in the injury/graft site of spinal cord in the MN + MT group 3 days after transplantation (Fig. 3c), suggesting that differentiating MSCs grafted can maintain the characteristic features of neural-like cells in the early period.Fig. 3


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)

Transdifferentiation of transplanted mesenchymal stem cell (MSC)-derived neural-like cells in the injury/graft site of spinal cord. a Some of the grafted MSCs transdifferentiated into myelin-forming cells (white arrowheads, adenomatous polyposis coli (APC)-positive and myelin basic protein (MBP)-positive) in the NT-3-MSC (MN) + TrkC-MSCs (MT) group, but not in the MSCs group, at 8 weeks after transplantation. b Pie charts show the percentage of APC-positive and MBP-positive cells from grafted MSC-derived neural-like cells. c Grafted MSC-derived neural-like cells lost their affinity for the neuron markers (Tju-1-negative and microtubule-associated protein 2 (Map2)-negative) at 8 weeks after transplantation. At 3 days, the grafted MSC-derived neural-like cells were intensely immunostained with neuron markers (white arrowheads, Tju-1-positive and Map2-positive) and some of them began to express myelin-forming cell maker (white arrowhead, APC-positive). Scale bars = 25 μm. Tju-1, β-tubulin III
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482203&req=5

Fig3: Transdifferentiation of transplanted mesenchymal stem cell (MSC)-derived neural-like cells in the injury/graft site of spinal cord. a Some of the grafted MSCs transdifferentiated into myelin-forming cells (white arrowheads, adenomatous polyposis coli (APC)-positive and myelin basic protein (MBP)-positive) in the NT-3-MSC (MN) + TrkC-MSCs (MT) group, but not in the MSCs group, at 8 weeks after transplantation. b Pie charts show the percentage of APC-positive and MBP-positive cells from grafted MSC-derived neural-like cells. c Grafted MSC-derived neural-like cells lost their affinity for the neuron markers (Tju-1-negative and microtubule-associated protein 2 (Map2)-negative) at 8 weeks after transplantation. At 3 days, the grafted MSC-derived neural-like cells were intensely immunostained with neuron markers (white arrowheads, Tju-1-positive and Map2-positive) and some of them began to express myelin-forming cell maker (white arrowhead, APC-positive). Scale bars = 25 μm. Tju-1, β-tubulin III
Mentions: At 8 weeks after surgical procedure, survival and distribution of grafted GFP-positive cells in GS scaffold were clearly evident in most of the injury/graft sites of spinal cords. Thus, 53.58 % of grafted GFP-positive cells expressed the mature oligodendrocyte marker APC (Fig. 3a,b), and 31.12 % of the cells expressed the other mature oligodendrocyte marker MBP (Fig. 3a,b) in the injury/graft site in the MN + MT group. On the other hand, APC- and MBP-positive cells were not observed in the MSC group (Fig. 3a). Interestingly, Tju-1- and MAP2-positive cells were not observed in the MSC and MN + MT groups (Fig. 3c). To further explore whether differentiating MSCs could maintain the neural-like cell phenotype in the early period of transplantation, neural markers of the MSCs grafted were examined in the MN + MT group. The results showed that Tju-1-, Map2-, and APC-positive cells were observed in the injury/graft site of spinal cord in the MN + MT group 3 days after transplantation (Fig. 3c), suggesting that differentiating MSCs grafted can maintain the characteristic features of neural-like cells in the early period.Fig. 3

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