PMID- 27862629 OWN - NLM STAT- MEDLINE DCOM- 20171219 LR - 20180331 IS - 1549-4918 (Electronic) IS - 1066-5099 (Linking) VI - 35 IP - 3 DP - 2017 Mar TI - Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity. PG - 641-653 LID - 10.1002/stem.2534 [doi] AB - Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, 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. In contrast, 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 combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, 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. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. 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. Stem Cells 2017;35:641-653. CI - (c) 2016 AlphaMed Press. FAU - Kano, Fumiya AU - Kano F AD - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. FAU - Matsubara, Kohki AU - Matsubara K AD - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. FAU - Ueda, Minoru AU - Ueda M AD - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. FAU - Hibi, Hideharu AU - Hibi H AD - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. FAU - Yamamoto, Akihito AU - Yamamoto A AD - Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161209 PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Sialic Acid Binding Immunoglobulin-like Lectins) RN - 0 (Siglec-9 protein, rat) SB - IM MH - Animals MH - Cell Differentiation MH - Cell Movement MH - *Cell Polarity MH - Cell Proliferation MH - Chemokine CCL2/*metabolism MH - Child MH - Facial Nerve/physiopathology MH - Female MH - Ganglia, Spinal/metabolism MH - Humans MH - Inflammation/pathology MH - Macrophages/metabolism/*pathology MH - Nerve Regeneration MH - Neuronal Outgrowth MH - Peripheral Nerves/*pathology/physiopathology MH - Rats, Sprague-Dawley MH - Recovery of Function MH - Schwann Cells MH - Sialic Acid Binding Immunoglobulin-like Lectins/*metabolism MH - Signal Transduction MH - Stem Cells/metabolism MH - Tooth, Deciduous/cytology OTO - NOTNLM OT - Dental pulp stem cells OT - Macrophages OT - Monocyte Chemoattractant Protein-1 OT - Peripheral nerve injury OT - Sialic acid-binding Ig-like lectin-9 EDAT- 2016/11/20 06:00 MHDA- 2017/12/20 06:00 CRDT- 2016/11/19 06:00 PHST- 2016/06/01 00:00 [received] PHST- 2016/09/30 00:00 [revised] PHST- 2016/10/10 00:00 [accepted] PHST- 2016/11/20 06:00 [pubmed] PHST- 2017/12/20 06:00 [medline] PHST- 2016/11/19 06:00 [entrez] AID - 10.1002/stem.2534 [doi] PST - ppublish SO - Stem Cells. 2017 Mar;35(3):641-653. doi: 10.1002/stem.2534. Epub 2016 Dec 9.