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Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation.

Lü HZ, Wang YX, Zhou JS, Wang FC, Hu JG - BMC Neurosci (2010)

Bottom Line: In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group.These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation.The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China.

ABSTRACT

Background: Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored.

Results: We transplanted green fluorescent protein (GFP) expressed OPCs (GFP-OPCs) into injured spinal cords of rats treated with or without CsA (10 mg/kg). Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI).

Conclusions: These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

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Three-dimensional reconstruction of lesion volumes at the 7th week after contusive SCI. A: Representatives of the three-dimensional reconstruction of a 10 mm spinal cord segment from each group containing the lesion cavity (green). The spinal cord contours and white matters are shown in semitransparent blue, and the gray matter is depicted in gray. B: Data are given as means ± SD, n = 6, * p < 0.05 (ANOVA).
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Figure 5: Three-dimensional reconstruction of lesion volumes at the 7th week after contusive SCI. A: Representatives of the three-dimensional reconstruction of a 10 mm spinal cord segment from each group containing the lesion cavity (green). The spinal cord contours and white matters are shown in semitransparent blue, and the gray matter is depicted in gray. B: Data are given as means ± SD, n = 6, * p < 0.05 (ANOVA).

Mentions: Quantitative analysis of the total lesion volume in whole spinal cords in all groups was performed at the 7th week after SCI. In the vehicle-treated group, the total lesion volume was 15.20% ± 1.97%. In the CsA-treated group, it was 11.23% ± 1.78%. In OPC transplantation with the vehicle-treated group, it was 14.89% ± 2.81%. In OPC transplantation with the CsA-treated group, it was 11.16% ± 1.83%. The total lesion volumes in CsA-treated groups (with or without OPC transplantation) were significantly lower than those of vehicle-treated groups (p < 0.05), while there was no difference between the two vehicle-treated groups or the two CsA-treated groups (with or without OPC transplantation) (Fig 5). These results indicate that CsA treatment can significantly decrease spinal cord lesion volume, while OPC transplantation has no effect.


Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation.

Lü HZ, Wang YX, Zhou JS, Wang FC, Hu JG - BMC Neurosci (2010)

Three-dimensional reconstruction of lesion volumes at the 7th week after contusive SCI. A: Representatives of the three-dimensional reconstruction of a 10 mm spinal cord segment from each group containing the lesion cavity (green). The spinal cord contours and white matters are shown in semitransparent blue, and the gray matter is depicted in gray. B: Data are given as means ± SD, n = 6, * p < 0.05 (ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959094&req=5

Figure 5: Three-dimensional reconstruction of lesion volumes at the 7th week after contusive SCI. A: Representatives of the three-dimensional reconstruction of a 10 mm spinal cord segment from each group containing the lesion cavity (green). The spinal cord contours and white matters are shown in semitransparent blue, and the gray matter is depicted in gray. B: Data are given as means ± SD, n = 6, * p < 0.05 (ANOVA).
Mentions: Quantitative analysis of the total lesion volume in whole spinal cords in all groups was performed at the 7th week after SCI. In the vehicle-treated group, the total lesion volume was 15.20% ± 1.97%. In the CsA-treated group, it was 11.23% ± 1.78%. In OPC transplantation with the vehicle-treated group, it was 14.89% ± 2.81%. In OPC transplantation with the CsA-treated group, it was 11.16% ± 1.83%. The total lesion volumes in CsA-treated groups (with or without OPC transplantation) were significantly lower than those of vehicle-treated groups (p < 0.05), while there was no difference between the two vehicle-treated groups or the two CsA-treated groups (with or without OPC transplantation) (Fig 5). These results indicate that CsA treatment can significantly decrease spinal cord lesion volume, while OPC transplantation has no effect.

Bottom Line: In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group.These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation.The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China.

ABSTRACT

Background: Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored.

Results: We transplanted green fluorescent protein (GFP) expressed OPCs (GFP-OPCs) into injured spinal cords of rats treated with or without CsA (10 mg/kg). Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI).

Conclusions: These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

Show MeSH
Related in: MedlinePlus