Development and Validation of a Multiparametric Semiquantitative Scoring System for the Histopathological Assessment of Ischaemia Severity in Skeletal Muscle

IF 3.1 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2023-03-16 DOI:10.1155/2023/5592455

C. Sanz-Nogués, M. Creane, S. Hynes, Xizhe Chen, C. A. Lagonda, K. Goljanek‐Whysall, Timothy O’Brien

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Abstract

Skeletal muscle is one of the most abundant and dynamic tissues of the body, with a strong regenerative capacity. Muscle injuries can occur as a result of a variety of events, including tissue ischaemia. Lower limb ischaemia occurs when there is an insufficient nutrient and oxygen supply, often caused by stenosis of the arteries due to atherosclerosis. The aim of this study was to develop and validate a multiparametric scoring tool for assessing ischaemia severity in skeletal muscle in a commonly used preclinical animal model. Tissue ischaemia was surgically induced in mice by ligation and excision of the femoral artery. Calf muscles were carefully dissected, prepared for histological analysis, and scored for inflammation, fibrosis, necrosis, adipocyte infiltration, and muscle fibre degeneration/regeneration. Kendall’s coefficient of concordance (W) showed a very good agreement between the appraisers when scoring each individual histological feature: inflammation (W = 0.92, p ≤ 0.001 ), fibrosis (W = 0.94, p ≤ 0.001 ), necrosis (W = 0.77, p ≤ 0.001 ), adipocyte infiltration (W = 0.91, p ≤ 0.001 ), and fibre degeneration/regeneration (W = 0.86, p ≤ 0.001 ). Intrarater agreement was also excellent (W = 0.94 or more, p ≤ 0.001 ). There was a statistically significant negative association between the level of muscle ischaemia damage and the calf muscle weight and skeletal muscle fibre diameter. Here, we have developed and validated a new multiparametric, semiquantitative scoring system for assessing skeletal muscle damage due to ischaemia, with excellent inter- and intrarater reproducibility. This scoring system can be used for assessing treatment efficacy in preclinical models of hind limb ischaemia.

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多参数半定量评分系统的开发和验证，用于骨骼肌缺血严重程度的组织病理学评估

骨骼肌是人体最丰富、最有活力的组织之一，具有很强的再生能力。肌肉损伤可能是多种事件的结果，包括组织缺血。下肢缺血发生在营养和氧气供应不足的情况下，通常是由动脉粥样硬化引起的动脉狭窄引起的。本研究的目的是开发和验证一种多参数评分工具，用于在常用的临床前动物模型中评估骨骼肌缺血严重程度。通过结扎和切除股动脉在小鼠中通过手术诱导组织缺血。仔细解剖小腿肌肉，准备进行组织学分析，并对炎症、纤维化、坏死、脂肪细胞浸润和肌肉纤维变性/再生进行评分。Kendall一致性系数（W）显示，评估人员在对每个组织学特征进行评分时非常一致：炎症（W = 0.92，p≤0.001），纤维化（W = 0.94，p≤0.001），坏死（W = 0.77，p≤0.001），脂肪细胞浸润（W = 0.91，p≤0.001），以及纤维变性/再生（W = 0.86，p≤0.001）。评分者内部一致性也很好（W = 0.94或更大，p≤0.001）。肌肉缺血损伤程度与小腿肌肉重量和骨骼肌纤维直径之间存在统计学上显著的负相关。在这里，我们开发并验证了一种新的多参数、半定量评分系统，用于评估缺血引起的骨骼肌损伤，具有良好的评分者间和评分者内再现性。该评分系统可用于评估后肢缺血临床前模型的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Tissue Engineering and Regenerative Medicine 生物-工程：生物医学

CiteScore

7.50

自引率

3.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.