Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy.

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING Journal of Tissue Engineering Pub Date : 2023-01-01 DOI:10.1177/20417314221139794
Charlotte Desprez, Davide Danovi, Charles H Knowles, Richard M Day
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Abstract

Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo.

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人类骨骼肌细胞的细胞形状特征作为肌生成能力的预测因子:一种精确细胞治疗的新范式。
骨骼肌源性细胞(SMDC)在补充因疾病或创伤而丧失的功能失调肌肉方面具有巨大的潜力。目前SMDC的治疗使用依赖于从肌肉活检中获取自体细胞,随后在体外扩增,然后再植入患者体内。异质性可能由多种因素引起,包括开始活检的质量、年龄和影响处理后SMDC的合并症。用于临床使用的质量属性通常集中在最低水平的肌源性细胞标志物表达。这些方法不能评估SMDC在体内植入后分化和形成肌纤维的可能性,而这最终决定了肌肉再生的可能性。在体外植入前预测SMDC的治疗效力是开发再生医学成功治疗方法和降低实施成本的关键。在这里,我们报告了一种新的SMDC分析工具的发展,用于检查来自不同供体的体外细胞群。我们开发了一个基于图像的管道来量化形态学特征和提取细胞形状描述符。我们研究了这些是否可以预测肌管形成的异质性,并与肌源性融合指数相关。发现一些早期细胞形状特征与融合指数呈负相关。这些指标包括细胞占据的总面积、面积形状、边界盒面积、密实度、等效直径、最小雪貂直径、小轴长度和初始培养后24 h的SMDC周长。通过我们的方法提取的信息表明,活细胞成像可以仅基于细胞形状检测一系列细胞表型,并且保持细胞完整性可用于预测体外形成肌管和体内功能组织的倾向。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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