open access

https://hdl.handle.net/2115/49108

Identification of Chemoattractive Factors Involved in the Migration of Bone Marrow-Derived Mesenchymal Stem Cells to Brain Lesions Caused by Prions

英語

2011-11

American Society for Microbiology

Journal of Virology

85(21)

11069-11078

Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions of neurodegenerative diseases; however, the precise mechanisms by which MSCs migrate remain to be elucidated. In this study, we carried out in vitro migration assay to investigate chemoattractive factors for MSCs in the brains of prion-infected mice. The migration of immortalized human MSCs (hMSCs) was reduced by their pre-treatment with antibodies against the chemokine receptors, CCR3, CCR5, CXCR3 and CXCR4 and by pre-treatment of brain extracts of prion-infected mice with antibodies against the corresponding ligands, suggesting the involvement of these receptors and their ligands in the migration of hMSCs. In agreement with the results of an in vitro migration assay, hMSCs in the corpus callosum, which are considered to be migrating from the transplanted area towards brain lesions of prion-infected mice, expressed CCR3, CCR5, CXCR3, and CXCR4. The combined in vitro and in vivo analyses suggest that CCR3, CCR5, CXCR3, and CXCR4, and their corresponding ligands are involved in the migration of hMSCs to the brain lesions caused by prion propagation. Additionally, hMSCs that had migrated to the right hippocampus of prion-infected mice expressed CCR1, CX3CR1, and CXCR4, implying the involvement of these chemokine receptors in hMSC functions after chemotactic migration. Further elucidation of the mechanisms that underlie the migration of MSCs may provide useful information regarding application of MSCs to the treatment of prion diseases.

学術雑誌論文

Accepted Manuscript

© 2011 American Society for Microbiology

0022-538X