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
| Autor: | Akihito Yamamoto, Kohki Matsubara, Hideharu Hibi, Fumiya Kano, Minoru Ueda |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular differentiation Neuronal Outgrowth Nerve fiber Biology Rats Sprague-Dawley 03 medical and health sciences Cell Movement Ganglia Spinal medicine Animals Humans Macrophage Peripheral Nerves Tooth Deciduous Child Chemokine CCL2 Cell Proliferation Inflammation Sialic Acid Binding Immunoglobulin-like Lectins Macrophages Stem Cells Monocyte Cell Polarity Cell Differentiation Recovery of Function Cell Biology M2 Macrophage Nerve Regeneration Cell biology Facial Nerve 030104 developmental biology medicine.anatomical_structure Ectodomain Immunology Peripheral nerve injury Molecular Medicine Female Schwann Cells Stem cell Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells. 35:641-653 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2534 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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