Repair of Traumatic Skeletal Muscle Injury with Bone-Marrow-Derived Mesenchymal Stem Cells Seeded on Extracellular Matrix

Abstract

Skeletal muscle injury resulting in tissue loss poses unique challenges for surgical repair. Despite the regenerative potential of skeletal muscle, if a significant amount of tissue is lost, skeletal myofibers will not grow to fill the injured area completely. Prior work in our lab has shown the potential to fill the void with an extracellular matrix (ECM) scaffold, resulting in restoration of morphology, but not functional recovery. To improve the functional outcome of the injured muscle, a muscle-derived ECM was implanted into a 1 x 1 cm(2), full-thickness defect in the lateral gastrocnemius (LGAS) of Lewis rats. Seven days later, bone-marrow-derived mesenchymal stem cells (MSCs) were injected directly into the implanted ECM. Partial functional recovery occurred over the course of 42 days when the LGAS was repaired with an MSC-seeded ECM producing 85.4 +/- 3.6% of the contralateral LGAS. This was significantly higher than earlier recovery time points (p < 0.05). The specific tension returned to 94 +/- 9% of the contralateral limb. The implanted MSC-seeded ECM had more blood vessels and regenerating skeletal myofibers than the ECM without cells (p < 0.05). The data suggest that the repair of a skeletal muscle defect injury by the implantation of a muscle-derived ECM seeded with MSCs can improve functional recovery after 42 days.

Engineering Approaches for Creating Skeletal Muscle

“…43 MSCs are used in a wide variety of treatment models, including both injectable and volumetric tissue engineered deliveries. 44,45 …”

Whole-organ engineering with natural extracellular materials

“…Likewise, improved muscle contractility force up to 85 % of pre-injury levels was seen after muscle-derived decellularized ECM was implanted in full-thickness defects in the lateral gastrocnemius of Lewis rats. Seven days post-injury, the implanted decellularized ECM were reseeded with bone--marrow-derived mesenchymal stem cells which led to the formation of new muscle tissue [37].…”

Surgical treatment for muscle injuries

“…Scaffolds cultivated with stem cells can regenerate the damaged muscle and can be a good option to improve performance after a muscle injury [29]. However, even if the scaffolds are used with no cells, it is possible to restore muscle function.…”