肌支架显示层粘连蛋白疤痕对干细胞功能有害,而肌跨度诱导代偿性纤维化。

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING
Kristen M Stearns-Reider, Michael R Hicks, Katherine G Hammond, Joseph C Reynolds, Alok Maity, Yerbol Z Kurmangaliyev, Jesse Chin, Adam Z Stieg, Nicholas A Geisse, Sophia Hohlbauch, Stefan Kaemmer, Lauren R Schmitt, Thanh T Pham, Ken Yamauchi, Bennett G Novitch, Roy Wollman, Kirk C Hansen, April D Pyle, Rachelle H Crosbie
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引用次数: 0

摘要

我们开发了一种载玻片脱细胞方法来生成脱细胞细胞外基质(ECM)肌支架,可以用各种细胞类型重新填充以询问细胞-ECM相互作用。利用这个平台,我们研究了纤维化的ECM瘢痕是否会影响人类骨骼肌祖细胞(SMPC)的功能,这是肌肉再生所必需的。SMPCs在健康肌肉来源的肌支架上表现出强大的粘附性、运动性和分化。所有SPMC与来自营养不良肌肉的纤维化肌支架的相互作用都严重减弱,包括运动率和迁移率降低。此外,SMPCs不能重塑病变肌支架内的层粘连蛋白致密纤维化疤痕。蛋白质组学和结构分析表明,过多的胶原沉积本身并不是病理性的,而且可以是代偿性的,正如营养不良肌肉中肌跨及其相关ECM受体的过度表达所揭示的那样。我们的体内数据也支持ECM重塑对SMPC植入很重要,纤维化疤痕可能是有效细胞治疗的一个障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis.

Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis.

We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.

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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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