Advanced Science (May 2022)

Application of an iPSC‐Derived Organoid Model for Localized Scleroderma Therapy

  • Jie Ma,
  • Wei Li,
  • Ruiyuan Cao,
  • Dunqin Gao,
  • Qiyu Zhang,
  • Xiao Li,
  • Biyou Li,
  • Luye Lv,
  • Mansheng Li,
  • Junyi Jiang,
  • Yujie Wang,
  • Jun Li,
  • Zhihong Wu,
  • Yunping Zhu,
  • Wu Zhong,
  • Shuyang Zhang,
  • Ling Leng

DOI
https://doi.org/10.1002/advs.202106075
Journal volume & issue
Vol. 9, no. 16
pp. n/a – n/a

Abstract

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Abstract Localized scleroderma (LoS) is a rare chronic disease with extensive tissue fibrosis, inflammatory infiltration, microvascular alterations, and epidermal appendage lesions. However, a deeper understanding of the pathogenesis and treatment strategies of LoS is currently limited. In the present work, a proteome map of LoS skin is established, and the pathological features of LoS skin are characterized. Most importantly, a human‐induced pluripotent stem cell‐derived epithelial and mesenchymal (EM) organoids model in a 3D culture system for LoS therapy is established. According to the findings, the application of EM organoids on scleroderma skin can significantly reduce the degree of skin fibrosis. In particular, EM organoids enhance the activity of epidermal stem cells in the LoS skin and promotes the regeneration of sweat glands and blood vessels. These results highlight the potential application of organoids for promoting the recovery of scleroderma associated phenotypes and skin‐associated functions. Furthermore, it can provide a new therapeutic alternative for patients suffering from disfigurement and skin function defects caused by LoS.

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