Background:

Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return to play with better function.

Purpose:

To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury.

Study Design:

Controlled laboratory study.

Methods:

Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 10⁵, and 2.5 × 10⁵ cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury.

Results:

The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 10⁵ cells, 2.5 × 10⁵ cells, 1.25 × 10⁵ cells plus F-127, and 2.5 × 10⁵ cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion.

Conclusion:

Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion.

Clinical Relevance:

Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.

中文翻译：

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骨髓间充质干细胞在小鼠挫伤后肌肉愈合中的应用。

背景：

骨骼肌损伤在运动医学中非常普遍。常规疗法的临床疗效有限。应该开发新的治疗方法，以使运动员能够以更好的状态恢复比赛。

目的：

评估骨髓来源的间充质干细胞的体外分化潜能以及间充质干细胞疗法对挫伤性损伤后肌肉愈合的体内组织学和生理学影响。

学习规划：

对照实验室研究。

方法：

从5周龄C57BL / 6小鼠的两只股骨中冲洗骨髓细胞，以建立永生化的间充质干细胞系。共使用36只8至10周的小鼠建立肌肉挫伤模型，并根据要注射的IM2细胞的不同剂量分为6组（每组6只小鼠）（0、1.25×10 ⁵，以及在100μL磷酸盐缓冲液中添加或不添加F-127的2.5×10 ^5个细胞）。进行肌肉再生的组织学分析，并在肌肉挫伤损伤后28天，在开始或之后14天注射不同剂量的间充质干细胞（不论是否带有F-127支架）后，测量肌肉收缩的快速抽搐和破伤风强度。挫伤。

结果：

经间充质干细胞处理的肌肉表现出许多再生的肌纤维。所有组均用间充质干细胞处理（1.25×10 ⁵细胞，2.5×10 ⁵细胞，1.25×10 ⁵细胞加F-127和2.5×10 ⁵与对照组和F-对照组相比，F-127细胞具有更高的再生肌纤维数量（平均±SD：分别为111.6±14.77、133.4±21.44、221.89±32.65和241.5±25.95）。 127（69±18.79和63.2±18.98）。快速抽搐和破伤风强度的生理评估未显示年龄相匹配的未受伤组与挫伤后28天用不同剂量的间充质干细胞治疗的组之间的差异。对照组与肌肉挫伤后不同剂量间充质干细胞治疗组之间存在显着差异。

结论：

在小鼠肌肉挫伤模型中，间充质干细胞疗法增加了再生肌纤维的数量，并改善了快速抽搐和破伤风的肌肉强度。但是，移植的间充质干细胞的快速衰变表明该作用具有旁分泌作用。用各种剂量的间充质干细胞结合F-127支架进行治疗是对肌肉挫伤的潜在疗法。

临床相关性：

间充质干细胞疗法对挫伤后肌纤维再生和肌肉力量有影响，因此对运动医学有作用。