title: Neural stem cells promote nerve regeneration through IL12-induced Schwann cell differentiation.
abstract: Regeneration of injured peripheral nerves is a slow, complicated process that could be improved by implantation of neural stem cells (NSCs) or nerve conduit. Implantation of NSCs along with conduits promotes the regeneration of damaged nerve, likely because (i) conduit supports and guides axonal growth from one nerve stump to the other, while preventing fibrous tissue ingrowth and retaining neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells and maintain a growth factor enriched microenvironment, which promotes nerve regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the cell extracts of implanted nerve conduit combined with NSCs by using protein antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6-fold higher than those in conduits without NSCs. In the sciatic nerve injury mouse model, implantation of NSCs combined with nerve conduit and IL12p80 improves motor recovery and increases the diameter up to 4.5-fold, at the medial site of the regenerated nerve. In vitro study further revealed that IL12p80 stimulates the Schwann cell differentiation of mouse NSCs through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that IL12p80 can trigger Schwann cell differentiation of mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and the diameter of regenerated nerves in a mouse sciatic nerve injury model.
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Don-Ching
authors.initials: DC
authors.lastname: Lee
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Jong-Hang
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Tai-Yu
authors.initials: TY
authors.lastname: Hsu
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Li-Hsun
authors.initials: LH
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hsu
authors.initials: H
authors.lastname: Chang
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chi
authors.affiliation: Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan; Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan. Electronic address: ingming@nhri.org.tw.
authors.forename: Ing-Ming
authors.initials: IM
authors.lastname: Chiu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018664:Interleukin-12 / Q000378:metabolism*; D051379:Mice; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D055495:Neurogenesis; D059348:Peripheral Nerve Injuries / Q000628:therapy*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology*; D012584:Sciatic Nerve / Q000502:physiology*; D033581:Stem Cell Transplantation
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D018664:Interleukin-12
keywords: IL12p80; Nerve conduit; Nerve regeneration; Neural stem cells; Schwann cells; Sciatic nerve injury