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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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Infiltration of CD3+T cells in the injured spinal cords. Two weeks after cell transplantation, immunofluorescence labeling showed the CD3+ T cells in injured spinal cords. A~D: Representative pictures show CD3+ cells in the vehicle (A), CsA (B), GFP-OPC transplantation with vehicle (C) or with CsA (D) groups. E: The statistical results. Data are given as means ± SD, n = 6, ** p < 0.01 (ANOVA). Scale bar 20 μm.
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Figure 3: Infiltration of CD3+T cells in the injured spinal cords. Two weeks after cell transplantation, immunofluorescence labeling showed the CD3+ T cells in injured spinal cords. A~D: Representative pictures show CD3+ cells in the vehicle (A), CsA (B), GFP-OPC transplantation with vehicle (C) or with CsA (D) groups. E: The statistical results. Data are given as means ± SD, n = 6, ** p < 0.01 (ANOVA). Scale bar 20 μm.

Mentions: To observe the effect of CsA on immune responses, we examined the infiltration of CD3+T cells, and activation of resident microglia and/or macrophages derived from infiltrating monocytes in the injured spinal cord at 2 weeks after cell transplantation. The CD3, a specific marker of T lymphocytes, and CD68, a marker of activated resident microglia and macrophages derived from infiltrating monocytes were detected by immunofluorescent staining. The numbers of CD3-positive cells in injured spinal cord of vehicle- and CsA-treated groups were 3,340 ± 355, and 958 ± 116, respectively, and of the OPC transplantation without and with CsA groups were 3261 ± 230, and 1037 ± 191, respectively (Fig. 3). The CD68-positive cells were 1485 ± 262, 309 ± 97, 1519 ± 328, and 326 ± 83, respectively (Fig. 4). The numbers of CD3-positive and CD68-positive cells in CsA-treated groups (with or without OPC transplantation) were significantly lower than those of vehicle-treated groups (p < 0.01), while the OPC transplantation had no effect on the infiltration of T cells and activation of microglia and/or macrophages derived from infiltrating monocytes (Fig 3E and Fig 4E).


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)

Infiltration of CD3+T cells in the injured spinal cords. Two weeks after cell transplantation, immunofluorescence labeling showed the CD3+ T cells in injured spinal cords. A~D: Representative pictures show CD3+ cells in the vehicle (A), CsA (B), GFP-OPC transplantation with vehicle (C) or with CsA (D) groups. E: The statistical results. Data are given as means ± SD, n = 6, ** p < 0.01 (ANOVA). Scale bar 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Infiltration of CD3+T cells in the injured spinal cords. Two weeks after cell transplantation, immunofluorescence labeling showed the CD3+ T cells in injured spinal cords. A~D: Representative pictures show CD3+ cells in the vehicle (A), CsA (B), GFP-OPC transplantation with vehicle (C) or with CsA (D) groups. E: The statistical results. Data are given as means ± SD, n = 6, ** p < 0.01 (ANOVA). Scale bar 20 μm.
Mentions: To observe the effect of CsA on immune responses, we examined the infiltration of CD3+T cells, and activation of resident microglia and/or macrophages derived from infiltrating monocytes in the injured spinal cord at 2 weeks after cell transplantation. The CD3, a specific marker of T lymphocytes, and CD68, a marker of activated resident microglia and macrophages derived from infiltrating monocytes were detected by immunofluorescent staining. The numbers of CD3-positive cells in injured spinal cord of vehicle- and CsA-treated groups were 3,340 ± 355, and 958 ± 116, respectively, and of the OPC transplantation without and with CsA groups were 3261 ± 230, and 1037 ± 191, respectively (Fig. 3). The CD68-positive cells were 1485 ± 262, 309 ± 97, 1519 ± 328, and 326 ± 83, respectively (Fig. 4). The numbers of CD3-positive and CD68-positive cells in CsA-treated groups (with or without OPC transplantation) were significantly lower than those of vehicle-treated groups (p < 0.01), while the OPC transplantation had no effect on the infiltration of T cells and activation of microglia and/or macrophages derived from infiltrating monocytes (Fig 3E and Fig 4E).

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