1. ¹Department of Molecular Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
2. ²Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan
3. ³Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
4. ⁴Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan

Correspondence: Hirofumi Hamada, Department of Molecular Medicine, Sapporo Medical University, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan. Fax: +81 (11) 611 2136. E-mail: hhamada@sapmed.ac.jp

Received 25 May 2004; Accepted 28 September 2004.

Abstract

Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.