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首页> 外文期刊>Orthopaedic Journal of Sports Medicine >Perivascular Stem Cells Diminish Muscle Atrophy and Retain Viability in a Rotator Cuff Tear Model
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Perivascular Stem Cells Diminish Muscle Atrophy and Retain Viability in a Rotator Cuff Tear Model

机译：大脑干细胞减少肌肉萎缩并在旋转袖口撕裂模型中保持活力

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Objectives: Rotator cuff tears (RCTs) are a common cause of shoulder pain and often necessitate surgical repair. Muscle changes including atrophy, fibrosis, and fatty degeneration can develop after RCTs, which may compromise surgical repair and clinical outcomes. Lipoaspirate-derived human perivascular stem cells (PSCs) have demonstrated myogenic and angiogenic potential in other small animal models of muscle injury. We hypothesized that the administration of PSCs following massive RCTs may help to diminish these muscle changes in a small animal model. Methods: A total of 90 immunodeficient mice were used (15 groups, N=6). Each was assigned to one of three surgical groups: i) sham, ii) supraspinatus and infraspinatus tendon transection (TT), or iii) TT and suprascapular nerve denervation (TT+DN). PSCs were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into small blood vessel residing pericytes (CD146+ CD34- CD45- CD31-) and large blood perivascular adventitial cells (CD146- CD34+ CD45- CD31-). Mice received either a) no injection, b) saline injection, c) pericyte injection, or d) adventitial cell injection at the time of the index procedure or at two weeks following index surgery. The supraspinatus muscles were harvested six weeks after the index procedure. Muscle atrophy was assessed by measuring percent wet muscle weight change for each sample. Muscle fiber cross-sectional area (CSA), fibrosis, and fatty degeneration were analyzed using Image J?. Additionally, pericytes and adventitial cells were transduced with a luciferase-containing construct. Animals were given injections of luciferin and imaged using IVIS to track in vivo bioluminescence following injections to assess cell viability. Results: Treatment with PSC injection after TT resulted in less wet weight loss and greater muscle fiber CSA than control groups (P<0.05). The TT+DN groups treated with PSC injections two weeks post-op also had less muscle weight loss and greater muscle fiber CSA than their respective control groups. The TT+DN groups treated with PSC injections at the time of surgery demonstrated no differences in weight loss, but had greater muscle fiber CSA than their respective controls. There was no difference in fibrosis between the TT groups. However, TT+DN groups treated with pericyte injections at both time points and adventitial cell injections two weeks post-op had less fibrosis than TT+DN controls. There was less fatty degeneration in the TT groups treated with pericyte injections at both time points and adventitial cells at the time of surgery compared to matched controls. There were no differences in the amount of fatty degeneration between the TT+DN groups. Bioluminescence imaging demonstrated viability of the injected cells at three weeks following injections (Figure 1). Conclusion: Our findings demonstrate significantly less muscle atrophy in the groups treated with PSC injections compared to respective controls for both TT and TT+DN procedures. These results suggest that the use of PSCs may have a role in the prevention of muscle atrophy by aiding in the maintenance of muscle bulk without leading to increased fibrosis or fatty infiltration. Additionally, bioluminescence data suggests that these cells maintain viability and engraft within the native muscle to improve muscle bulk. Improved muscle quality in the setting of rotator cuff tears may increase the success rates of rotator cuff repair and lead to superior clinical outcomes.
机译：目的：转子袖口撕裂（RCT）是肩痛的常见原因，往往需要手术修复。肌肉变化包括萎缩，纤维化和脂肪变性在RCT后可以发育，这可能会损害手术修复和临床结果。 Lipoashirate衍生的人血管血管干细胞（PSCs）在肌肉损伤的其他小动物模型中表明了肌菌和血管生成潜力。我们假设大规模RCT后PSC的给药可能有助于减少小动物模型中的这些肌肉变化。方法：使用总共90只免疫缺少小鼠（15组，N = 6）。每组分为三种外科手术组中的一种：i）假，ii）Supraspinatus和Inthaspinatus肌腱转育（TT），或III）TT和初产腺神经去除（TT + DN）。将PSC从人脂肪痉挛中收获，并使用荧光激活的细胞分选成小血管停留围网（CD146 + CD34-CD31-）和大型血血病患者患有大血管患者（CD146- CD34 + CD45-CD31-）。小鼠在指数手术期间或在指数手术后两周内或在指数手术后两周内，未注射，B）盐液注射，C）盐液注射，或D）患者注射液。在指数程序后六周收获冈上肌肉。通过测量每个样品的湿肌肉重量百分比来评估肌肉萎缩。使用Image J分析肌纤维横截面积（CSA），纤维化和脂肪变性。另外，用含荧光素酶的构建体转导细胞和过度细胞。将动物注射注射荧光素并使用IVIS进行成像，以在注射后进行体内生物发光以评估细胞活力。结果：PSC注射治疗TT后导致湿重量损失较小，肌肉纤维CSA比对照组更小（P <0.05）。用PSC注射治疗的TT + DN组两周后OP的肌肉减肥和较大的肌纤维CSA少于其各自的对照组。在手术时用PSC注射治疗的TT + DN组证明了重量损失没有差异，但具有比各自的对照更大的肌纤维CSA。 TT组之间的纤维化没有差异。然而，在OP后两周的时间点和过度细胞注射治疗的TT + DN组在OP后两周的纤维化少于TT + DN控制。与匹配的对照相比，在手术时，在手术时在手术时在两次时间点和患有周期细胞处理的TT组中脂肪变性较少。 TT + DN组之间的脂肪变性的量没有差异。生物发光成像在注射后三周内显示出注入的细胞的活力（图1）。结论：与TT和TT + DN程序的各个对照相比，我们的研究结果表明，用PSC注射治疗的组中的肌萎缩显着较低。这些结果表明，使用PSCs的使用可能在防止肌肉散装中预防肌肉萎缩而没有导致增加纤维化或脂肪浸润。另外，生物发光数据表明这些细胞在天然肌肉内保持活力和嵌入肌肉，以改善肌肉散装。改善旋转箍撕裂的肌肉质量可能会增加转子袖带修复的成功率，并导致优越的临床结果。

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