Abstract
Background: We previously identified mouse interleukin-12p80 (mIL12p80, a homodimer of IL12p40) in the cell extracts of implanted poly(L-lactic acid) (PLA) nerve conduit combined with neural stem cells (NSCs) and showed that mIL12p80 enhances the functional recovery and nerve regeneration in mice. Here, we showed that human IL12p80 (hIL12p80) improves the sciatic nerve regeneration in mice. Methods: Implantation of hIL12p80 and NSCs into nerve conduit promotes repair of the sciatic nerve injury in mouse model. Findings: NSCs transplanted with hIL12p80 showed the best recovery than the other groups in sciatic functional index (SFI), compound muscle action potential (CMAP) and Rotarod analyses. In addition, the group with Conduit+NSC+hIL12p80 (CNI) outperformed the other groups in SFI and Rotarod tests beginning at the fourth-week post-surgery. Immunohistochemistry showed that the CNI group increases the diameter of newly regenerated nerve 98%. In vitro studies showed that hIL12p80 stimulates differentiation of mouse NSCs to oligodendrocyte lineages through phosphorylation of Stat3 at Y705. Further, implantation using poly(L-lactic-co-glycolic acid) (PLGA) nerve conduits (C 2.0 and C 2.1) showed better recovery in Rotarod test and CMAP than using PLA conduits (C 1.0) in FVB/NJ (FVB) mice. In C57BL/6J (B6) mice, the group with C 2.1+NSC+hIL12p80 (C 2.1NI) not only promotes sciatic functional recovery but also reduces experimental autotomy. Interpretation: These results suggest that hIL12p80 together with NSCs enhance the functional recovery and accelerate the regeneration of damaged nerves in mice. These findings could be used in devising potential strategies for nerve injury treatment. Funding Statement: This research is supported by National Health Research Institutes, Taiwan (CS-107-PP-02), and Ministry of Science and Technology, Taiwan (107-1901-01-19-03; 107-0324-01-19-03). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: In this study, all animal experimental procedures followed ethical guidelines and were approved by the Institutional Animal Care and Use Committee (IACUC) of the National Health Research Institutes (Protocol No. NHRI-IACUC-101067A).
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