<p>Inadequate tendon healing and heterotopic bone formation result in substantial pain and disability, yet the specific cells responsible for tendon healing remain uncertain. Here we identify a CD26<sup>+</sup> tendon stem/progenitor cells residing in peritendon, which constitutes a primitive stem cell population with self-renewal and multipotent differentiation potentials. CD26<sup>+</sup> tendon stem/progenitor cells migrate into the tendon midsubstance and differentiation into tenocytes during tendon healing, while ablation of these cells led to insufficient tendon healing. Additionally, CD26<sup>+</sup> tendon stem/progenitor cells contribute to heterotopic ossification and Tenascin-C-Hippo signaling is involved in this process. Targeting Tenascin-C significantly suppresses chondrogenesis of CD26<sup>+</sup> tendon stem/progenitor cells and subsequent heterotopic ossification. Our findings provide insights into the identification of tendon stem/progenitor cells and illustrate the essential role of CD26<sup>+</sup> tendon stem/progenitor cells in tendon healing and heterotopic bone formation.</p>

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A CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification

  • Siwen Chen,
  • Yingxin Lin,
  • Hao Yang,
  • Zihao Li,
  • Sifang Li,
  • Dongying Chen,
  • Wenjun Hao,
  • Shuai Zhang,
  • Hua Chao,
  • Jingyu Zhang,
  • Jianru Wang,
  • Zemin Li,
  • Xiang Li,
  • Zhongping Zhan,
  • Hui Liu

摘要

Inadequate tendon healing and heterotopic bone formation result in substantial pain and disability, yet the specific cells responsible for tendon healing remain uncertain. Here we identify a CD26+ tendon stem/progenitor cells residing in peritendon, which constitutes a primitive stem cell population with self-renewal and multipotent differentiation potentials. CD26+ tendon stem/progenitor cells migrate into the tendon midsubstance and differentiation into tenocytes during tendon healing, while ablation of these cells led to insufficient tendon healing. Additionally, CD26+ tendon stem/progenitor cells contribute to heterotopic ossification and Tenascin-C-Hippo signaling is involved in this process. Targeting Tenascin-C significantly suppresses chondrogenesis of CD26+ tendon stem/progenitor cells and subsequent heterotopic ossification. Our findings provide insights into the identification of tendon stem/progenitor cells and illustrate the essential role of CD26+ tendon stem/progenitor cells in tendon healing and heterotopic bone formation.