Improved motor function in dko mice by intravenous transplantation of bone marrow-derived mesenchymal stromal cells.

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.

• Authors: Zhong Li, Hong-Ying Liu, Qing-Feng Lei, Cheng Zhang, Shu-Nong Li
• Journal: Cytotherapy (Cytotherapy) Vol. 13 Issue 1 Pg. 69-77 (Jan 2011) ISSN: 1477-2566 [Electronic] England
• PMID: 20735169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dystrophin
• Utrophin

Topics

• Animals
• Bone Marrow Cells (cytology)
• Cells, Cultured
• Dystrophin (metabolism)
• Flow Cytometry
• Fluorescent Antibody Technique
• Genotype
• Injections, Intravenous
• Kaplan-Meier Estimate
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology)
• Mice
• Mice, Knockout
• Motor Activity (physiology)
• Muscle, Striated (pathology, physiopathology)
• Muscular Dystrophy, Animal (pathology, physiopathology, therapy)
• Rats
• Rats, Sprague-Dawley
• Rotarod Performance Test
• Stromal Cells (cytology, transplantation)
• Utrophin (metabolism)