In vivo testing of an injectable matrix gel for the treatment of shoulder cuff muscle fatty degeneration.
In vivo testing of an injectable matrix gel for the treatment of shoulder cuff muscle fatty degeneration.
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用于治疗肩袖肌肉脂肪变性的可注射基质凝胶的体内测试。
DOI：
10.1016/j.jse.2020.03.038
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发表时间：
2020-12
影响因子：
3
通讯作者：
Wolchok JC
中科院分区：
文献类型：
--
作者：
Huynh T;Kim JT;Dunlap G;Ahmadi S;Wolchok JC
细胞外基质（ECM）凝胶已经显示出治疗受损组织（最显著的是心肌）的功效。我们假设从骨骼肌中制备的ECM凝胶可以用作脂肪肩袖肌肉变性的治疗策略。我们进行了以下实验：1）使用大鼠模型评估ECM凝胶注射的宿主生物相容性; 2）使用兔模型检查ECM凝胶注射对释放的冈上肌（SSP）肌腱延迟修复后肌肉恢复的影响。宿主与ECM凝胶的生物相容性的特征在于与巨噬细胞浸润、基质沉积和炎性细胞因子产生相关的几种基因的瞬时升高（仅前两周）。到8周时，所有基因都恢复到基线水平，并且从组织学上没有观察到纤维化或慢性炎症的证据。当凝胶注射与SSP肌腱修复结合时，我们观察到与仅用肌腱修复治疗（减少31 ± 7%）相比，SSP肌肉萎缩显著减少（减少7%）（从未受伤减少24 ± 3%）。虽然两个治疗组的脂肪变性均升高，但与仅肌腱修复（6.1 ± 2.9%）相比，肌腱修复联合肌内ECM注射（4.1 ± 2.1%）的脂肪含量呈下降趋势（2%）。转录组分析显示仅修复组中脂肪形成和骨关节炎途径激活。这些关键途径在使用联合修复加凝胶的治疗中被废除。研究结果表明，ECM注射对肌肉质量、脂肪变性和关键细胞信号通路有适度但积极的影响。
Extracellular matrix (ECM) gels have shown efficacy for the treatment of damaged tissues, most notably cardiac muscle. We hypothesized that the ECM gel prepared from skeletal muscle could be used as a treatment strategy for fatty shoulder cuff muscle degeneration. We conducted experiments to 1) evaluate host biocompatibility to ECM gel injection using a rat model; and 2) examine the effect of ECM gel injection on muscle recovery following delayed repair of a released supraspinatus (SSP) tendon using a rabbit model. The host biocompatibility to ECM gel was characterized by a transient rise (first two weeks only) in several genes associated with macrophage infiltration, matrix deposition, and inflammatory cytokine production. By eight weeks all genes had returned to baseline levels and no evidence of fibrosis or chronic inflammation was observed from histology. When gel injection was combined with SSP tendon repair, we observed a significant reduction (7%) in SSP muscle atrophy (24+3% reduction from uninjured) when compared to treatment with tendon repair only (31+7% reduction). While fatty degeneration was elevated in both treatment groups, fat content trended lower (2%) in response to combined tendon repair and intramuscular ECM injection (4.1+2.1%) when compared to tendon repair only (6.1+2.9%). Transcriptome analysis revealed adipogenesis and osteoarthritis pathway activation in the repair only group. These key pathways were abrogated in response to treatment using combined repair plus gel. The findings suggest that ECM injection had a modest but positive effect on muscle mass, fatty degeneration, and key cellular signaling pathways.
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影响因子：
2.9
作者：
Hoashi S;Hinenoya T;Tanaka A;Ohsaki H;Sasazaki S;Taniguchi M;Oyama K;Mukai F;Mannen H
通讯作者：
Mannen H
影响因子：
3.1
作者：
DeQuach JA;Lin JE;Cam C;Hu D;Salvatore MA;Sheikh F;Christman KL
通讯作者：
Christman KL
DOI：
10.1186/2052-1847-6-41
发表时间：
2014
期刊：
BMC sports science, medicine & rehabilitation
影响因子：
--
作者：
Aurora A;Garg K;Corona BT;Walters TJ
通讯作者：
Walters TJ
影响因子：
14
作者：
Hurd, Shiloh A.;Bhatti, Nadia M.;Walker, Addison M.;Kasukonis, Ben M.;Wolchok, Jeffrey C.
通讯作者：
Wolchok, Jeffrey C.
影响因子：
7.2
作者：
Dziki, Jenna;Badylak, Stephen;Rubin, J. Peter
通讯作者：
Rubin, J. Peter