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Therapeutic effect of autologous compact bone-derived mesenchymal stem cell transplantation on prion disease

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Title: Therapeutic effect of autologous compact bone-derived mesenchymal stem cell transplantation on prion disease
Authors: Shan, Zhifu Browse this author
Hirai, Yuji Browse this author
Nakayama, Momoko Browse this author
Hayashi, Ryo Browse this author
Yamasaki, Takeshi Browse this author
Hasebe, Rie Browse this author →KAKEN DB
Song, Chang-Hyun Browse this author
Horiuchi, Motohiro Browse this author →KAKEN DB
Keywords: prions
mesemchymal stem cells
regenerative medicine
Issue Date: Oct-2017
Publisher: Society for General Microbiology
Journal Title: Journal of general virology
Volume: 98
Issue: 10
Start Page: 2615
End Page: 2627
Publisher DOI: 10.1099/jgv.0.000907
PMID: 28874230
Abstract: Prion diseases are fatal neurodegenerative disorders of humans and animals and no effective treatments are currently available. Allogenic transplantation of immortalized human mesenchymal stem cells (MSCs) can prolong the survival of mice infected with prions. However, autologous transplantation is an appropriate model for evaluating the effects of MSCs on prion diseases. Therefore, we isolated and purified MSCs from the femur and tibia of mice as compact bone-derived MSCs (CB-MSCs). Flow cytometric analysis showed that CB-MSCs were negative for myeloid stem cell-derived cell markers CD11b and CD45, but positive for molecules such as Sca-1, CD105 and CD90.2, which are reported to be expressed on MSCs. The ability of CB-MSCs to migrate to brain extracts from prion-infected mice was confirmed by an in vitro migration assay. Intrahippocampus transplantation of CB-MSCs at 120 days post-inoculation marginally but significantly prolonged the survival of mice infected with the Chandler prion strain. The transplantation of CB-MSCs did not influence the accumulation of diseasespecific prion protein. However, the CB-MSC transplantation enhanced microglial activation, which appeared to be polarized to the M2-type activation state. These results suggest that autologous MSC transplantation is a possible treatment for prion diseases, while the modification of microglial activation may be a therapeutic target for neurodegenerative diseases.
Type: article (author version)
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 堀内 基広

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