Fe3O4@Polydopamine-Labeled MSCs Targeting the Spinal Cord to Treat Neuropathic Pain Under the Guidance of a Magnetic Field

Abstract

Meichen Liu,1 Weijia Yu,2 Fuqiang Zhang,2 Te Liu,2 Kai Li,1 Meng Lin,3 Ying Wang,2 Guoqing Zhao,1 Jinlan Jiang2 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Guoqing Zhao; Jinlan Jiang No. 126, Xiantai Street, Changchun City, Jilin Province, People’s Republic of ChinaEmail [email protected]; [email protected]: Neuropathic pain causes great distress among patients; however, its response to traditional analgesia techniques remains sub-optimal. There has been progress in stem cell research for neuropathic pain treatment; however, effective homing remains problematic. This study aimed to establish Fe3O4@polydopamine(PDA)-labeled mesenchymal stem cells (MSCs); moreover, we aimed to guide MSCs using a magnetic field to the spinal cord segments showing pain-related responses to allow MSC homing and gathering, in advance, in order to fully employ their repair function.Materials and Methods: Fe3O4@PDA-labeled MSCs were characterized using transmission electron microscopy. We analyzed the characteristics of MSCs, as well as the nanoparticle effects on MSC activity, differentiation, and proliferation, using the CCK-8 method, flow cytometry, and staining. Using rats, we performed behavioral tests of mechanical and thermal pain hypersensitivity. Serum inflammatory markers were detected using ELISA. Finally, changes in proteins associated with spinal cord pain were detected through quantitative reverse transcription PCR, histology, and immunohistochemistry.Results: Fe3O4@PDA did not affect the characteristics and viability of MSCs. The magnetic field guidance improved the therapeutic effect of Fe3O4@PDA-labeled MSCs as indicated by the paw withdrawal threshold. Fe3O4@PDA-labeled MSCs decreased spinal nerve demyelination and c-Fos expression (a pain molecule); moreover, they inhibited microglia and astrocyte activation.Conclusion: Fe3O4@PDA-labeled MSCs showed better homing to the spinal cord under magnetic field guidance. Moreover, they inhibited microglial and astrocyte activation, as well as played an early and continuous role in neuropathic pain treatment.Keywords: Fe3O4@PDA, MSCs, neuropathic pain, microglia, astrocytes

Keywords

• fe3o4@pda
• mscs
• neuropathic pain
• microglia
• astrocytes.