2024-03-28T14:58:59Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00023238
2023-01-16T04:12:58Z
499:500:501
Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity
Matsubara, Kohki
68981
Matsushita, Yoshihiro
68982
Sakai, Kiyoshi
68983
Kano, Fumiya
68984
Kondo, Megumi
68985
Noda, Mariko
68986
Hashimoto, Noboru
68987
Imagama, Shiro
68988
Ishiguro, Naoki
68989
Suzumura, Akio
68990
Ueda, Minoru
68991
Furukawa, Koichi
68992
Yamamoto, Akihito
68993
anti-inflammation
dental pulp stem cells
macrophage polarity
MCP-1
Siglec-9
spinal cord injury
Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.
journal article
Society for Neuroscience
2015-02
application/pdf
The Journal of Neuroscience
6
35
2452
2464
https://doi.org/10.1523/JNEUROSCI.4088-14.2015
http://hdl.handle.net/2237/25433
0270-6474
https://nagoya.repo.nii.ac.jp/record/23238/files/2452_full.pdf
eng
https://doi.org/10.1523/JNEUROSCI.4088-14.2015
Copyright(c)2015 the authors