Graft alignment impacts the regenerative response of skeletal muscle after volumetric muscle loss in a rat model.
Graft alignment impacts the regenerative response of skeletal muscle after volumetric muscle loss in a rat model.
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DOI：
10.1016/j.actbio.2020.01.024
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发表时间：
2020-03-15
影响因子：
9.7
通讯作者：
Wolchok J
中科院分区：
文献类型：
--
作者：
Kim J;Kasukonis B;Roberts K;Dunlap G;Brown L;Washington T;Wolchok J
在容积性肌肉丢失(VML)损伤的病因学中的一个关键事件是由潜在的细胞外基质(ECM)提供的结构线索的大量丢失。为了重新建立丢失的线索，文献中有广泛的共识支持使用植入式支架。然而，尽管基于支架的再生医学策略已经显示出潜力，但在整个领域观察到的结果仍有相当大的可变性。我们认为，结果可变性的一个被忽视的来源是脚手架架构的差异。这项研究的目的是验证假说，即种植体对齐对VML损伤修复后的基因和表型结果有显著影响。使用大鼠VML模型，检测三个自体种植体治疗组(对准种植体、45°错位和90°错位)和两个恢复时间点(2周和12周)的结果(n=6-8个/组)。在修复后2周，治疗组的肌肉质量和扭矩恢复率没有显著差异，但我们确实观察到MyoD(2.5倍)和Pax7(2倍)基因表达显著上调，以及植入部位存在未成熟的肌纤维。在修复后12周，可以检测到治疗组之间的功能和结构差异。对齐的自体移植物的质量和扭矩恢复率(77±10%)显著高于45°和90°未对齐的自体移植物(分别为±10%和61±11%)。组织结构检查显示，只有那些使用错位自体移植物治疗的动物，才有广泛的纤维化和非收缩组织面积百分比的显着增加。综上所述，这些结果表明，植入物的取向对体内结果有显著的影响，并表明移植物对齐对肌肉表型的影响可能是通过损伤和修复部位的肌肉生成和纤维化的基因改变来调节的。
A key event in the etiology of volumetric muscle loss (VML) injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). To re-establish the lost cues, there is broad consensus within the literature supporting the utilization of implantable scaffolding. However, while scaffold based regenerative medicine strategies have shown potential, there remains a significant amount of outcome variability observed across the field. We suggest that an overlooked source of outcome variability is differences in scaffolding architecture. The goal of this study was to test the hypothesis that implant alignment has a significant impact on genotypic and phenotypic outcomes following the repair of VML injuries. Using a rat VML model, outcomes across three autograft implant treatment groups (aligned implants, 45° misaligned, and 90° misaligned) and two recovery time points (2 weeks and 12 weeks) were examined (n=6–8/group). At 2 weeks post-repair there were no significant differences in muscle mass and torque recovery between the treatment groups, however we did observe a significant upregulation of MyoD (2.5 fold increase) and Pax7 (2 fold increase) gene expression as well as the presence of immature myofibers at the implant site for those animals repaired with aligned autografts. By 12 weeks post-repair, functional and structural differences between the treatment groups could be detected. Aligned autografts had significantly greater mass and torque recovery (77±10% of normal) when compared to 45° and 90° misaligned autografts (64±10% and 61±11%, respectively). Examination of tissue structure revealed extensive fibrosis and a significant increase in non-contractile tissue area fraction for only those animals treated using misaligned autografts. When taken together, the results suggest that implant graft orientation has a significant impact on in-vivo outcomes and indicate that the effect of graft alignment on muscle phenotype may be mediated through genotypic changes to myogenesis and fibrosis at the site of injury and repair.
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影响因子：
4.1
作者：
Kim, John T.;Kasukonis, Benjamin;Wolchok, Jeffrey C.
通讯作者：
Wolchok, Jeffrey C.
影响因子：
46.9
作者：
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通讯作者：
Atala, Anthony
DOI：
10.1016/j.bbrc.2019.06.082
发表时间：
2019-08-20
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
4.9
作者：
Browe, Daniel;Freeman, Joseph
通讯作者：
Freeman, Joseph
影响因子：
14
作者：
Costantini, Marco;Testa, Stefano;Gargioli, Cesare
通讯作者：
Gargioli, Cesare