2. Academic Validation
  3. Engineered MSC Aggregates with E/N-Cadherin and IL-6 Preconditioning for the Treatment of Systemic Sclerosis

Engineered MSC Aggregates with E/N-Cadherin and IL-6 Preconditioning for the Treatment of Systemic Sclerosis

  • Adv Healthc Mater. 2025 Jun 11:e2500663. doi: 10.1002/adhm.202500663.
Yue Zhang 1,  Mengyuan Qian 2,  Yirui Shi 3,  Jiaxu Cao 2,  Min Xu 4,  Xin Wen 5,  Yunxia Yan 5,  Sha Liu 4,  Hongwei Chen 4,  Shanshan Liu 5,  Jun Yang 2,  Lingyun Sun 3 6
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, 321 Zhongshan Road, Nanjing, 210008, P. R. China.
  • 2 The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, 94 Weijin Road, Tianjin, 300071, P. R. China.
  • 3 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, 321 Zhongshan Road, Nanjing, 210008, P. R. China.
  • 4 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, 210008, P. R. China.
  • 5 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, P. R. China.
  • 6 Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, P. R. China.
PMID: 40500954 DOI: 10.1002/adhm.202500663
Abstract

Umbilical cord-derived mesenchymal stromal cells (MSCs) transplantation is a promising therapy for systemic sclerosis (SSc) because of their distinctive antifibrotic and immunomodulatory properties. To enhance the effects of MSCs transplantation, novel engineered MSC aggregates preconditioned with human E/N-Cadherin fusion protein (hE/N-cad-Fc) and interleukin-6 (IL-6) for SSc treatment are fabricated and named 3D-Cad/IL6-MSCs. These novel-engineered MSC aggregates possess tighter cellular cohesion and exhibit enhanced antiapoptotic, immunosuppressive, and proangiogenic capabilities according to transcriptomic analyses. Moreover, 3D-Cad/IL6-MSCs have improved immunoregulatory effects on peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and CD8+ T cells in vitro because of the synergistic preconditioning from IL-6 and bioactive hE/N-cad-Fc. Upon intravenous injection, 3D-Cad/IL6-MSCs significantly mitigate skin and lung fibrosis and prolong the retention duration in bleomycin (BLM)-induced SSc mouse model. In detail, they suppress excessive infiltration of macrophages and T cells in the injured skin and lungs and reestablish the immune equilibrium of circulating CD4+ T-cell subsets in vivo. These results suggest that 3D-Cad/IL6-MSCs are ideal candidates for SSc therapy and optimize the clinical utilization of MSCs.

Keywords

IL‐6; aggregates; cadherin; mesenchymal stromal cells; systemic sclerosis.

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