Development of regenerative therapy against severe peripheral nerve injury with a novel anti-inflammatory M2 macrophages inducer derived from dental pulp stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293427
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: The University of Tokushima (2016-2017); Nagoya University (2014-2015)
• Principal Investigator: YAMAMOTO Akihito 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (50244083)
• Co-Investigator(Kenkyū-buntansha): 伊佐 正 生理学研究所, 発達生理学研究系認知行動発達機構研究部門, 教授 (20212805) ; 上田 実 名古屋大学, 医学(系)研究科(研究院), 教授 (00151803)
• Research Collaborator: KANO Fumiya
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 歯髄幹細胞 / 末梢神経再生

Outline of Final Research Achievements

We show that an implantation of the serum‐free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED‐CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. SHED‐CM specifically depleted of a set of anti‐inflammatory M2 macrophage inducers, monocyte chemoattractant protein‐1 (MCP‐1) and the secreted ectodomain of sialic acid‐binding Ig‐like lectin‐9 (sSiglec‐9) lost the ability to restore neurological function in this model. Notably, the implantation of a collagen graft containing MCP‐1/sSiglec‐9 into the nerve gap induced anti‐inflammatory M2 macrophage polarization, generated a Schwann‐cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. Taken together, our data suggest that MCP‐1/sSiglec‐9 regenerates PNs by inducing tissue‐repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries.

Free Research Field

再生医学