A latent Axin2⁺/Scx⁺ progenitor pool is the central organizer of tendon healing.

IF 6.4 1区医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2024-10-17 DOI:10.1038/s41536-024-00370-2

Mor Grinstein, Stephanie L Tsai, Daniel Montoro, Benjamin R Freedman, Heather L Dingwall, Steffany Villaseñor, Ken Zou, Moshe Sade-Feldman, Miho J Tanaka, David J Mooney, Terence D Capellini, Jayaraj Rajagopal, Jenna L Galloway

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Abstract

A tendon's ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx⁺/Axin2⁺ population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2⁺ cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2⁺-descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2⁺ identity. Specific loss of Wnt secretion in Axin2⁺ or Scx⁺ cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2⁺/Scx⁺ cells rely on self-regulation to maintain their identity as key organizers of tissue healing.

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潜伏的 Axin2+/Scx+ 祖细胞池是肌腱愈合的核心组织者。

肌腱有序的细胞外基质（ECM）对传递力量至关重要，但也极易受伤。目前还不太清楚嵌入这种致密 ECM 内和周围的肌腱细胞是如何协调愈合的。在这里，我们在小鼠和人类肌腱中发现了一种特化的静止Scx+/Axin2+细胞群，它能启动愈合，是修复的主要功能贡献者。Axin2+细胞表达干细胞标记，体外扩增，并具有多线分化潜能。肌腱损伤后，Axin2+后裔细胞渗入损伤部位，增殖并分化成腱细胞。将Axin2标记的细胞移植到损伤肌腱中的试验显示，它们具有显著增殖和分化的双重能力，但仍能保持其Axin2+特性。Axin2+或Scx+细胞Wnt分泌的特异性丧失会破坏它们对损伤做出反应的能力，严重影响愈合。我们的工作凸显了一种不寻常的模式，即特化的Axin2+/Scx+细胞依靠自我调节来保持其作为组织愈合关键组织者的特性。

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

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

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.