Intraosseous transplant of dystrophin expressing chimeric (DEC) cells improves skeletal muscle function in mouse model of Duchenne muscular dystrophy.

INTRODUCTION

We previously reported that systemic delivery of dystrophin expressing chimeric (DEC) cells of normal () and dystrophin-deficient () myoblast (MB) or mesenchymal stem cell (MSC) origin restored dystrophin expression and improved cardiac function in the mouse model of Duchenne muscular dystrophy (DMD).

AIM

This study evaluated the effect of intraosseous delivery of murine DEC lines of MB (MB /MB ) and MSC (MB /MSC ) origin on function of gastrocnemius muscle (GM).

MATERIAL AND METHODS

DEC lines created by fusion were tested in the mouse model of DMD: Group 1 - vehicle (control), Group 2 - non-fused 0.25 × 10 MB and 0.25 × 10 MSC (control), Group 3 - fused 0.5 × 10 MB /MB DEC and Group 4 - fused 0.5 × 10 MB /MSC DEC. and muscle force tests assessed GM function at 90 days post-transplant.

RESULTS

Application of MB /MSC and MB /MB DEC significantly improved the fatigue ratio of GM compared to vehicle-injected controls detected by muscle force tests (0.567 ±0.116, = 0.045 and 0.489 ±0.087, < 0.05, respectively). MB /MSC DEC recipients presented enhanced maximum force at tetanus (0.145 ±0.040 g/mg, < 0.05); furthermore, recipients of MB /MB DEC showed a significant increase in the maximum force generation rate compared to vehicle controls (4.447 ±1.090 g/s/mg, < 0.05). The GM force testing in MB /MSC DEC recipients detected increased average GM force compared to vehicle and non-fused controls.

CONCLUSIONS

Systemic-intraosseous administration of MB /MB and MB /MSC DEC therapy combining the myogenic and immunomodulatory properties of MB and MSC significantly improved skeletal muscle (GM) function of force and resistance to fatigue in an mouse model of DMD.