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Journal of Virology, June 2009, p. 5918-5927, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00165-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells on Mice Infected with Prions{triangledown} ,{dagger}

Chang-Hyun Song,1 Osamu Honmou,2 Natsuo Ohsawa,1 Kiminori Nakamura,3 Hirofumi Hamada,3 Hidefumi Furuoka,4 Rie Hasebe,1 and Motohiro Horiuchi1*

Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818,1 Departments of Neural Repair and Therapeutics,2 Molecular Medicine, Sapporo Medical University, South-1st, West-16th, Chuo-ku, Sapporo 060-8543,3 Department of Pathobiological Science, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080-8555, Japan4

Received 23 January 2009/ Accepted 9 March 2009

Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions in experimental models of ischemia, tumors, and neurodegenerative diseases and to ameliorate functional deficits. In this study, we attempted to evaluate the therapeutic potential of MSCs for treating prion diseases. Immortalized human MSCs (hMSCs) that express the LacZ gene were transplanted into the unilateral hippocampi or thalami of mice, and their distributions were monitored by the expression of β-galactosidase. In mice infected with prions, hMSCs transplanted at 120 days postinoculation (dpi) were detected on the contralateral side at 2 days after transplantation and existed there even at 3 weeks after transplantation. In contrast, few hMSCs were detected on the contralateral side for mock-infected mice. Interestingly, the migration of hMSCs appeared to correlate with the severity of neuropathological lesions, including disease-specific prion protein deposition. The hMSCs also migrated to a prion-specific lesion in the brain, even when intravenously injected. Although the effects were modest, intrahippocampal and intravenous transplantation of hMSCs prolonged the survival of mice infected with prions. A subpopulation of hMSCs in the brains of prion-infected mice produced various trophic factors and differentiated into cells of neuronal and glial lineages. These results suggest that MSCs have promise as a cellular vehicle for the delivery of therapeutic genes to brain lesions associated with prion diseases and, furthermore, that they may help to regenerate neuronal tissues damaged by prion propagation.

* Corresponding author. Mailing address: Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan. Phone and fax: 81-11-706-5293. E-mail: horiuchi{at}vetmed.hokudai.ac.jp

{triangledown} Published ahead of print on 18 March 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, June 2009, p. 5918-5927, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00165-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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