論文

査読有り 国際誌
2020年1月8日

Transplantation of M2-Deviated Microglia Promotes Recovery of Motor Function after Spinal Cord Injury in Mice.

Molecular therapy : the journal of the American Society of Gene Therapy
  • Shuhei Kobashi
  • ,
  • Tomoya Terashima
  • ,
  • Miwako Katagi
  • ,
  • Yuki Nakae
  • ,
  • Junko Okano
  • ,
  • Yoshihisa Suzuki
  • ,
  • Makoto Urushitani
  • ,
  • Hideto Kojima

28
1
開始ページ
254
終了ページ
265
記述言語
英語
掲載種別
DOI
10.1016/j.ymthe.2019.09.004

Despite the poor prognosis of spinal cord injury (SCI), effective treatments are lacking. Diverse factors regulate SCI prognosis. In this regard, microglia play crucial roles depending on their phenotype. The M1 phenotype exacerbates neuroinflammation, whereas the M2 phenotype promotes tissue repair and provides anti-inflammatory effects. Therefore, we compared the effects of M2 and M1 microglia transplantation on SCI. First, we established a method for effective induction of M1 or M2 microglia by exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-4, respectively, to be used for transplantation in a SCI mouse model. In the M2 microglia transplantation group, significant recovery of motor function was observed compared with the control and M1 groups. Elevated transcription of several neuroprotective molecules including mannose receptor C type 1 (Mrc1), arginase 1 (Arg1), and insulin-like growth factor 1 (Igf1) was observed. Moreover, intramuscular injection of FluoroRuby dye revealed recovery of retrograde axonal transport from the neuromuscular junction to upstream of the injured spinal cord only in the M2-transplanted group, although the number of migrated microglia were comparable in both M1 and M2 groups. In conclusion, our results indicated that M2 microglia obtained by IL-4 stimulation may be a promising candidate for cell transplantation therapy for SCI.

リンク情報
DOI
https://doi.org/10.1016/j.ymthe.2019.09.004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31604678
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952178
ID情報
  • DOI : 10.1016/j.ymthe.2019.09.004
  • PubMed ID : 31604678
  • PubMed Central 記事ID : PMC6952178

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