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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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Identification and differentiation of GFP-OPCs. The GFP-OPCs induced from spinal cord-derived NPCs were cultured in different media for 5 days. (A~C): In the basal-OPC-medium containing PDGF and bFGF, the cells display bipolar or tri-polar morphology, the typical morphology of OPC (A), more than 95% of cells express both A2B5 (B) and PDGFR (C). Inserts show higher power photographs of OPCs. (D~I) In the medium containing T3 and without PDGF and bFGF, the cells display a multipolar morphology (D, G), more than 95% of the cells express RIP (E, F), and almost no cells express GFAP (H, I).(J~O) In the medium containing 10%FBS without PDGF and bFGF, the cells display the typical process-bearing morphology of astrocytes (J, M), few cells express RIP (K, L) and nearly all cells express GFAP (N, O). Cells in B, C, E, F, H, I, K, L, N and O were counterstained with Hoechst33342 (blue), a nuclear dye. Scale bars: 25 μm.
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Figure 1: Identification and differentiation of GFP-OPCs. The GFP-OPCs induced from spinal cord-derived NPCs were cultured in different media for 5 days. (A~C): In the basal-OPC-medium containing PDGF and bFGF, the cells display bipolar or tri-polar morphology, the typical morphology of OPC (A), more than 95% of cells express both A2B5 (B) and PDGFR (C). Inserts show higher power photographs of OPCs. (D~I) In the medium containing T3 and without PDGF and bFGF, the cells display a multipolar morphology (D, G), more than 95% of the cells express RIP (E, F), and almost no cells express GFAP (H, I).(J~O) In the medium containing 10%FBS without PDGF and bFGF, the cells display the typical process-bearing morphology of astrocytes (J, M), few cells express RIP (K, L) and nearly all cells express GFAP (N, O). Cells in B, C, E, F, H, I, K, L, N and O were counterstained with Hoechst33342 (blue), a nuclear dye. Scale bars: 25 μm.

Mentions: GFP-OPCs were cultured for 5 days in different media as described in Materials and Methods, to assess their differentiation potential. When oligospheres were triturated into single cells and plated onto coverslips in basal-OPC-medium supplied with PDGF-AA and bFGF (+PDGF, +bFGF), almost all of the cells displayed bipolar or tri-polar morphology, the typical morphology of OPCs (Fig. 1A). Among them, more than 95% of cells expressed both A2B5 and PDGFRα (Fig. 1B, C). In the presence of T3 without PDGF-AA and bFGF (-PDGF, -bFGF, +T3), the cells displayed a multi-polar morphology (Fig. 1D, G). More than 95% of them expressed RIP (Fig. 1E, F), and almost no cells expressed GFAP (Fig. 1H, I). In the presence of 10% FBS (-PDGF, -bFGF, +10%FBS), the cells displayed the typical process-bearing morphology of astrocytes (Fig. 1J, M). Few cells expressed RIP (Fig. 1K, L) and nearly all cells expressed GFAP (Fig. 1N, O).


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)

Identification and differentiation of GFP-OPCs. The GFP-OPCs induced from spinal cord-derived NPCs were cultured in different media for 5 days. (A~C): In the basal-OPC-medium containing PDGF and bFGF, the cells display bipolar or tri-polar morphology, the typical morphology of OPC (A), more than 95% of cells express both A2B5 (B) and PDGFR (C). Inserts show higher power photographs of OPCs. (D~I) In the medium containing T3 and without PDGF and bFGF, the cells display a multipolar morphology (D, G), more than 95% of the cells express RIP (E, F), and almost no cells express GFAP (H, I).(J~O) In the medium containing 10%FBS without PDGF and bFGF, the cells display the typical process-bearing morphology of astrocytes (J, M), few cells express RIP (K, L) and nearly all cells express GFAP (N, O). Cells in B, C, E, F, H, I, K, L, N and O were counterstained with Hoechst33342 (blue), a nuclear dye. Scale bars: 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Identification and differentiation of GFP-OPCs. The GFP-OPCs induced from spinal cord-derived NPCs were cultured in different media for 5 days. (A~C): In the basal-OPC-medium containing PDGF and bFGF, the cells display bipolar or tri-polar morphology, the typical morphology of OPC (A), more than 95% of cells express both A2B5 (B) and PDGFR (C). Inserts show higher power photographs of OPCs. (D~I) In the medium containing T3 and without PDGF and bFGF, the cells display a multipolar morphology (D, G), more than 95% of the cells express RIP (E, F), and almost no cells express GFAP (H, I).(J~O) In the medium containing 10%FBS without PDGF and bFGF, the cells display the typical process-bearing morphology of astrocytes (J, M), few cells express RIP (K, L) and nearly all cells express GFAP (N, O). Cells in B, C, E, F, H, I, K, L, N and O were counterstained with Hoechst33342 (blue), a nuclear dye. Scale bars: 25 μm.
Mentions: GFP-OPCs were cultured for 5 days in different media as described in Materials and Methods, to assess their differentiation potential. When oligospheres were triturated into single cells and plated onto coverslips in basal-OPC-medium supplied with PDGF-AA and bFGF (+PDGF, +bFGF), almost all of the cells displayed bipolar or tri-polar morphology, the typical morphology of OPCs (Fig. 1A). Among them, more than 95% of cells expressed both A2B5 and PDGFRα (Fig. 1B, C). In the presence of T3 without PDGF-AA and bFGF (-PDGF, -bFGF, +T3), the cells displayed a multi-polar morphology (Fig. 1D, G). More than 95% of them expressed RIP (Fig. 1E, F), and almost no cells expressed GFAP (Fig. 1H, I). In the presence of 10% FBS (-PDGF, -bFGF, +10%FBS), the cells displayed the typical process-bearing morphology of astrocytes (Fig. 1J, M). Few cells expressed RIP (Fig. 1K, L) and nearly all cells expressed GFAP (Fig. 1N, O).

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