Mitochondrial Fusion Protein 2-Modified Bone Marrow Mesenchymal Stem Cells Improved Hyperglycemia-Induced Schwann Cell Injury via Regulating Mitochondria-Associated Endoplasmic Reticulum Membranes.

OBJECTIVE: High glucose damages rat Schwann cells (SCs), which is closely related to the dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAMs). Therefore, the present study aimed to investigate the protective effects and mechanisms of modified bone marrow mesenchymal stem cells (BMSCs) and mitochondrial fusion protein 2 (Mfn2) modified BMSCs against SCs injury. METHODS: The Mfn2-modified BMSCs were constructed after culturing with neural-induced differentiation solution. MAP-2 (microtubule-associated protein-2, neuron marker) and GFAP (glial fibrillary acidic protein, astrocytes marker) immunofluorescence staining was used to observe changes in the differentiation potential of neural-like BMSCs. SCs (RSC96) cells cultured under high glucose conditions were cocultured with Mfn2-modified BMSCs. Changes in functional protein expression of MAMs were detected by Western Blot. Transmission electron microscopy (TEM) was used to observe the microscopic morphology of MAMs, mitochondria and endoplasmic reticulum. RESULTS: The expression level of Mfn2 was significantly increased in BMSCs transfected with Mfn2. The fluorescence densities of MAP-2 and GFAP were significantly upregulated in Mfn2-BMSCs after induction by neural inducible differentiation solution. When RSC96 was incubated with high glucose and Mfn2-modified/non-modified BMSCs, the expression level of Mfn2 in RSC96 was significantly increased, while PERK, IP3R and Drp1 expressions were significantly reduced. And the Mfn2-modified BMSCs showed more significant effects comparing to Mfn2-non-modified BMSCs. The TEM showed the structural integrity of MAMs, clear structure of mitochondrial cristae and obvious and structurally intact extension of endoplasmic reticulum in Mfn2-BMSC group. CONCLUSIONS: Mfn2 transfection promoted neural-like cell differentiation in BMSCs. Mfn2-modified BMSCs modulated the structural and functional homeostasis of MAMs by regulating the expression levels of MAMs functional proteins.