The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

J Biomed Mater Res A. 2024 Jul;112(7):1025-1040. doi: 10.1002/jbm.a.37687. Epub 2024 Feb 16.

Abstract

The current evidence provides support for the involvement of bone marrow mesenchymal stem cells (BMSCs) in the regulation of airway epithelial cells. However, a comprehensive understanding of the underlying biological mechanisms remains elusive. This study aimed to isolate and characterize BMSC-derived exosomes (BMSC-Exos) and epithelial cells (ECs) through primary culture. Subsequently, the impact of BMSC-Exos on ECs was assessed in vitro, and sequencing analysis was conducted to identify potential molecular mechanisms involved in these interactions. Finally, the efficacy of BMSC-Exos was evaluated in animal models in vivo. In this study, primary BMSCs and ECs were efficiently isolated and cultured, and high-purity Exos were obtained. Upon uptake of BMSC-Exos, ECs exhibited enhanced proliferation (p < .05), while migration showed no difference (p > .05). Notably, invasion demonstrated significant difference (p < .05). Sequencing analysis suggested that miR-21-5p may be the key molecule responsible for the effects of BMSC-Exos, potentially mediated through the MAPK or PI3k-Akt signaling pathway. The in vivo experiments showed that the presence of methacrylated gelatin (GelMA) loaded with BMSC-Exos in composite scaffold significantly enhanced epithelial crawling in the patches in comparison to the pure decellularized group. In conclusion, this scheme provides a solid theoretical foundation and novel insights for the research and clinical application of tracheal replacement in the field of tissue engineering.

Keywords: epithelial cells; exosomes; molecular mechanism; orthotopic tracheal transplantation; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Epithelial Cells* / cytology
  • Epithelial Cells* / metabolism
  • Exosomes* / metabolism
  • Gelatin* / chemistry
  • Gelatin* / pharmacology
  • Humans
  • Male
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Methacrylates / chemistry
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Tissue Scaffolds* / chemistry

Substances

  • Gelatin
  • Methacrylates
  • MicroRNAs