Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury.
Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury.
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DOI：
10.1038/s41420-018-0027-8
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发表时间：
2018-12
影响因子：
7
通讯作者：
Corona BT
中科院分区：
文献类型：
--
作者：
Aguilar CA;Greising SM;Watts A;Goldman SM;Peragallo C;Zook C;Larouche J;Corona BT
骨骼肌在受伤时具有显著的再生能力，但当面临导致肌肉体积损失（VML）的重大创伤性损伤时，再生过程始终失败。VML损伤导致的肌肉组织和功能丧失促使开发了一套治疗方法，但这些策略在没有全面了解驱动损伤反应的分子景观的情况下进行。在此，我们在已建立的啮齿动物模型中给予VML损伤，并使用肌肉功能测试、组织学和通过RNA测序的表达谱来监测愈合现象在多个时间点的演变。然后将损伤反应与使用自体切碎的肌肉移植物（~1 mm 3组织碎片）的原位移植的再生医学治疗进行比较。在VML后的所有时间点均观察到慢性炎症和纤维化反应。这些结果表明，在愈合反应的急性阶段对VML损伤的病理反应破坏了内源性和治疗性再生过程。总体而言，所提供的数据描绘了VML损伤的病理生物学反应的关键分子特征，这些特征是有效再生治疗范例的关键效应物。
Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1 mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms.
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