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Stem Cells, Neuronal and Glial Production/Differentiation

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Injury-induced stem cells can differentiate into microglia

  • P2-072
  • 河原 麻衣子 / Maiko Kawahara:1,2 川村 美貴 / Miki Kawamura:2,3 中込 隆之 / Takayuki Nakagomi:2 佐久間 理香 / Rika Sakuma:2 八木 秀司 / Hideshi Yagi:4 松山 知弘 / Tomohiro Matsuyama:2 
  • 1:関西学院大学大学院 / Kwansei Gakuin University , Hyogo, Japan 2:兵庫医科大学先端医学研究所神経再生研究部門 / Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan 3:大阪大学大学院 / Osaka University , Osaka, Japan 4:兵庫医科大学解剖学神経科学部門 / Anatomy and Neuroscience, Hyogo Collage of Medicine , Hyogo, Japan 

It is now accepted that microglia are derived from myeloid precursors. It has been reported that some hematopoietic stem cells in the early embryo are precursors of microglia. On the other hand, a subclass of microglia has a potential to transdifferentiate into neurons and oligodendrocytes, suggesting the microglia as multipotent stem cells. Independently we already have isolated neural stem/progenitor cells induced by cerebral ischemia (iNSPC) which are derived from vascular pericytes and express some hematopoietic markers. In the present study, we examined whether iNSPC would have a potential to differentiate into microglia as well as neural cells. Permanent cerebral ischemia was produced by occluding middle cerebral artery of CB-17 mice. The ischemic tissue was removed 3 days after the insult, and dissociated by passage through needles. The cell suspensions were incubated in attached medium consisting of bFGF. Then MACS-sorted PDGFRβ-positive cells were cultured in neurosphere-producing medium. Some of spheroids obtained were subjected to immunocytochemistry, and others were followed by differentiation into neural lineage and microglia. Phagocytosis of these cells was examined by using the Assay Kit. Immunocytochemistry showed that all cells in the spheroids expressed nestin, PDGFRβ, α-SMA and NG2. Iba1 and CD11b were strongly expressed in these cells, but CD68 was very weakly stained. Spheroid cultured for 4 weeks differentiated into a neuron, astrocyte and oligodendrocyte in serum-free medium. Alternatively, spheroid cultured for less than 2 weeks in same medium predominantly differentiated into microglia-like cells expressing Iba1 and CD11b. These cells showed phagocytosis when latex beads are added in the medium. These results suggest that PDGFRβ-positive pericytes after stroke can differentiate into microglia as well as neural lineage, i.e. all components of CNS. Although the precise mechanism for transdifferentiation of pericytes is still unknown, the present study suggests the iNSPC as an origin of microglia proliferating in injured brain and new mechanism for repairing CNS.

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