Abstract
Background. Significant and/or complete rupture in the musculotendinous junction (MTJ) is a challenging lesion to treat because of the lack of reliable suture methods. Skeletal muscle-derived multipotent stem cell (Sk-MSC) sheet-pellets, which are able to reconstitute peripheral nerve and muscular/vascular tissues with robust connective tissue networks, have been applied as a “bio-bond”.Methods. Sk-MSC sheet-pellets, derived from GFP transgenic-mice after 7 days of expansion culture, were detached with EDTA to maintain cell–cell connections. A completely ruptured MTJ model was prepared in the right tibialis anterior (TA) of the recipient mice, and was covered with sheet-pellets. The left side was preserved as a contralateral control. The control group received the same amount of the cell-free medium. The sheet-pellet transplantation (SP) group was further divided into two groups; as the short term (4–8 weeks) and long term (14–18 weeks) recovery group. At each time point after transplantation, tetanic tension output was measured through the electrical stimulation of the sciatic nerve. The behavior of engrafted GFP+ tissues and cells was analyzed by fluorescence immunohistochemistry.Results. The SP short term recovery group showed average 64% recovery of muscle mass, and 36% recovery of tetanic tension output relative to the contralateral side. Then, the SP long term recovery group showed increased recovery of average muscle mass (77%) and tetanic tension output (49%). However, the control group showed no recovery of continuity between muscle and tendon, and demonstrated increased muscle atrophy, with coalescence to the tibia during 4–8 weeks after operation. Histological evidence also supported the above functional recovery of SP group. Engrafted Sk-MSCs primarily formed the connective tissues and muscle fibers, including nerve-vascular networks, and bridged the ruptured tendon–muscle fiber units, with differentiation into skeletal muscle cells, Schwann cells, vascular smooth muscle, and endothelial cells.Discussion. This bridging capacity between tendon and muscle fibers of the Sk-MSC sheet-pellet, as a “bio-bond,” represents a possible treatment for various MTJ ruptures following surgery.
Highlights
Skeletal muscles represent muscle–tendon complexes attached to the bone
Muscle injuries can be classified as ruptures, tears, and lacerations, typically caused by external hard compression or excessive stretching forces, and they are categorized into 3 grades of severity, as follows: Grade-I injury affects only a limited number of fibers in the muscle, and the strength does not decrease in the full active and passive range of motions, with pain and tenderness being delayed until the day; Grade-II injury, where nearly half of muscle fibers are torn, and acute and significant pain is accompanied by swelling and a minor decrease in muscle strength; Grade-III injury, with the complete rupture of the muscle, where the injured muscle is torn into 2 parts, together with severe swelling and pain, and a total loss of function
A close relationship of GFP+ cells and muscle fibers, nerve axons, and the neuromuscular junctions was evident (Fig. 6F, in the dotted line circle as α-bungarotoxin+), confirming that GFP+ cells contributed to peripheral nerve extensions, reaching to the end of a motor nerve. These results indicate that the transplanted GFP+ Skeletal muscle-derived multipotent stem cell (Sk-MSC) sheet-pellets mainly form connective tissue networks together with a certain amount of muscle fibers, and that they physically bind the tendon and muscle fibers, contributing to the peripheral nerve-blood vessel formation
Summary
Skeletal muscles represent muscle–tendon complexes attached to the bone. due to their roles in the protection of the body and the force generation at the body-movements, injuries invariably occur during various activities or as a result of accidents. Several suturing techniques have been reported for the treatment of complete tendon rupture (Hirpara et al, 2007; Maquirriain, 2011; Merolla et al, 2009; Rawson, Cartmell & Wong, 2013; Yildirim et al, 2006), but there is a lack of reliable suture methods for the ruptures that involve the muscle belly or MTJ (Faibisoff & Daniel, 1981; Kragh et al, 2005c; Oliva et al, 2013; Phillips & Heggers, 1988). The SP short term recovery group showed average 64% recovery of muscle mass, and 36% recovery of tetanic tension output relative to the contralateral side. This bridging capacity between tendon and muscle fibers of the Sk-MSC sheet-pellet, as a ‘‘bio-bond,’’ represents a possible treatment for various MTJ ruptures following surgery
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