Osteoimmune Modulation and Guided Osteogenesis Promoted by Barrier Membranes Incorporated with S-Nitrosoglutathione (GSNO) and Mesenchymal Stem Cell-Derived Exosomes

Int J Nanomedicine. 2020 May 15:15:3483-3496. doi: 10.2147/IJN.S248741. eCollection 2020.

Abstract

Background: The use of polycaprolactone (PCL) for bone defects in a clinical setting is limited due to a lack of bioactivity. Exosomes derived from mesenchymal stem cells (MSCs) have an important immunoregulatory potential and together with S-nitrosoglutathione (GSNO) they possess therapeutic potential for bone regeneration.

Materials and methods: In this study, PCL was modified with GSNO and MSC-derived exosomes and the impact on macrophages and osteogenes is evaluated.

Results: MSC-derived exosomes exhibited a cup-shaped morphology and were internalized by macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs). The pattern of internalization of scaffold-immobilized exosomes was similar in RAW264.7 cells and hBMSCs after 4h and 24h of co-culture. Assessment of macrophage morphology under inflammatory conditions by scanning electronic microscopy (SEM) and confocal microscopy demonstrated macrophages were significantly elongated and expression of pro-inflammatory genes markedly decreased when co-cultured with PCL/PDA + GSNO + exosome scaffolds. Furthermore, this scaffold modification significantly enhanced osteogenic differentiation of hBMSCs.

Discussion: This study demonstrated the possibility of using a GSNO- and exosome-based strategy to adapt barrier membrane scaffolds. PCL/PDA + GSNO + exosome scaffolds may serve as an important barrier membrane for osteogenesis and tissue regeneration.

Keywords: S-nitrosoglutathione; exosomes; mesenchymal stem cells; osteogenesis; polycaprolactone.

MeSH terms

  • Animals
  • Cell Differentiation
  • Endocytosis
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Humans
  • Inflammation / pathology
  • Macrophages / pathology
  • Macrophages / ultrastructure
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Osteogenesis*
  • RAW 264.7 Cells
  • S-Nitrosoglutathione / metabolism*
  • Tissue Scaffolds / chemistry

Substances

  • S-Nitrosoglutathione