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. 2017:2017:6352858.
doi: 10.1155/2017/6352858. Epub 2017 Feb 19.

Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

Shuyun Zhang  1 , Baolin Shi  1
Affiliations

Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

Shuyun Zhang et al. Biomed Res Int. 2017.

Abstract

Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

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Conflict of interest statement

The authors declare that there is no conflict of interests regarding the publication of this paper.

Figures

Figure 1
Figure 1
Establishment of diabetic model rats and isolation of SC. (a) The average body weight of rats in the control group increased time-dependently, while that in diabetes group almost kept constant. (b) After induction, the average concentration of blood glucose of rats in diabetes group was generally much higher than in control group. (c) SC isolated from sciatic nerve expressed S-100 protein.
Figure 2
Figure 2
EPO overexpression MSC provided protection of SC derived from the periphery nerve of diabetic rat. (a) The schematic illustration of coculture of MSC and SC; (b) the cellular GSH level, (c) the cell viability, and (d) the cell apoptosis of SC in different groups; ∗P < 0.05; ∗∗P < 0.01.
Figure 3
Figure 3
Expressions of apoptosis related proteins in SC indirect cocultivated with MSC-EPO. The protein expressions of their apoptosis related proteins, including p-Akt, cleaved caspase-3, Bcl-2, and Bax, were investigated by western blotting. ∗∗P < 0.01 compared with normal group; ##P < 0.01 compared with diabetic group; &&P < 0.01 compared with diabetic + MSC group; &P < 0.05 compared with diabetic + MSC group.
Figure 4
Figure 4
Apoptosis of SC directly cocultivated with MSC-EPO. The cellular apoptosis of SC in different groups was assessed by TUNEL staining. ∗∗P < 0.01 compared with normal group; ##P < 0.01 compared with diabetic group; &&P < 0.01 compared with diabetic + MSC group.
Figure 5
Figure 5
Under High glucose culture condition, indirect coculture with MSC-EPO provided protection of SC derived from diabetic rat. (a) The schematic illustration of indirect coculture of MSC and SC; (b) the cellular GSH level, (c) the cell viability, and (d) the cell apoptosis of SC in different groups; ∗P < 0.05; ∗∗P < 0.01.
Figure 6
Figure 6
Expressions of apoptosis related proteins in SC indirect cocultivated with MSC-EPO under high glucose culture condition. The protein expressions of their apoptosis related proteins, including p-Akt, cleaved caspase-3, Bcl-2, and Bax, were investigated by western blotting. ∗∗P < 0.01 compared with normal group; ##P < 0.01 compared with diabetic group; &&P < 0.01 compared with diabetic + MSC group.
Figure 7
Figure 7
Apoptosis of SC directly cocultivated with MSC-EPO in high glucose culture condition. The cellular apoptosis of SC in different groups was assessed by TUNEL staining. ∗P < 0.05 compared with diabetic group; ##P < 0.01 compared with diabetic + high glucose group; &&P < 0.01 compared with diabetic + high glucose + MSC group.
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