Abstract
Background aims. We explored the potential therapeutic value of transplanting bone marrow (BM)-derived mesenchymal stromal cells (MSC) into utrophin/dystrophin-deficient double knock-out (dko) mice, a murine model of Duchenne muscular dystrophy. Methods. MSC from male rats were isolated and transplanted into female dko mice via the caudal vein. Behavior and locomotor function were later evaluated, along with the expression of dystrophin and utrophin in the sarcolemma of myofiber tissues. The presence of grafted cells was confirmed via polymerase chain reaction for the sex-determining region of the Y-chromosome. Results. Locomotor activity improved significantly (P < 0.05) from 5 to 15 weeks after cell transplantation, as measured by traction, rotating rod and running wheel tests. We also found that the expression of dystrophin and utrophin increased significantly (P < 0.05) and progressively in the sarcolemma from 5 to 15 weeks after transplantation. The median lifespan of mice in the normal group (74.1 weeks) was significantly (P < 0.001) higher than those in the control (22.0 weeks) and transplantation (35.0 weeks) groups, and the median lifespan of mice in the transplantation group was significantly (P < 0.001) higher than that in the control group. Conclusions. Results of this study demonstrate that BM MSC have potential value in xenogeneic transplantation therapy for muscular dystrophy.
Acknowledgments
We thank Professor K. E. Davies (Genetics Unit, Department of Biochemistry, University of Oxford, Oxford, UK) for the generous gift of three pairs of utrophin/dystrophin-deficient mice. This study was supported by the National Natural Science Foundation of China (numbers 30270732, 30170337 and 30000057) and the Foundation for Science & Technology of Guangzhou, China (number 2002J1-C0182).
Disclosure of interest: This research article is not under review at any other publication. All co-authors have read and agree with the contents of this manuscript and have no actual or potential financial conflicts of interest to report.