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体积性肌肉损失与治疗性支架植入的小鼠模型。

A mouse model of volumetric muscle loss and therapeutic scaffold implantation.

作者信息

Hu Caroline, Chiang Gladys, Chan Alex H-P, Alcazar Cynthia, Nakayama Karina H, Quarta Marco, Rando Thomas A, Huang Ngan F

机构信息

Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.

The Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA, USA.

出版信息

Nat Protoc. 2025 Mar;20(3):608-619. doi: 10.1038/s41596-024-01059-y. Epub 2024 Oct 18.

Abstract

Skeletal myofibers naturally regenerate after damage; however, impaired muscle function can result in cases when a prominent portion of skeletal muscle mass is lost, for example, following traumatic muscle injury. Volumetric muscle loss can be modeled in mice using a surgical model of muscle ablation to study the pathology of volumetric muscle loss and to test experimental treatments, such as the implantation of acellular scaffolds, which promote de novo myogenesis and angiogenesis. Here we provide step-by-step instructions to perform full-thickness surgical ablation, using biopsy punches, and to remove a large volume of the tibialis anterior muscle of the lower limb in mice. This procedure results in a reduction in muscle mass and limited regeneration capacity; the approach is easy to reproduce and can also be applied to larger animal models. For therapeutic applications, we further explain how to implant bioscaffolds into the ablated muscle site. With adequate training and practice, the surgical procedure can be performed within 30 min.

摘要

骨骼肌纤维在受损后可自然再生;然而,当骨骼肌质量的很大一部分丧失时,例如在创伤性肌肉损伤后,肌肉功能可能会受损。可以使用肌肉消融手术模型在小鼠中模拟体积性肌肉损失,以研究体积性肌肉损失的病理并测试实验性治疗方法,如植入促进从头肌生成和血管生成的无细胞支架。在这里,我们提供了使用活检打孔器进行全层手术消融并切除小鼠下肢胫骨前肌大量组织的分步说明。该操作会导致肌肉质量减少和再生能力受限;该方法易于重复,也可应用于更大的动物模型。对于治疗应用,我们进一步解释了如何将生物支架植入消融的肌肉部位。经过充分的培训和练习,该手术可在30分钟内完成。

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