Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Apoptosis, TNF Alpha and Interferon Gamma Response Gene mRNA Expression in T Lymphocytes

Andrea Fracchia, Drirh Khare, Samar Da’na, Reuven Or, Amnon Buxboim, Boaz Nachmias, Claudine Barkatz, Regina Golan-Gerstl, Swasti Tiwari, Polina Stepensky, Yuval Nevo, Hadar Benyamini, Sharona Elgavish, Osnat Almogi-Hazan, Batia Avni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have highlighted the therapeutic potential of small extracellular bodies derived from mesenchymal stem cells (MSC-sEVs) for various diseases, notably through their ability to alter T-cell differentiation and function. The current study aimed to explore immunomodulatory pathway alterations within T cells through mRNA sequencing of activated T cells cocultured with bone marrow-derived MSC-sEVs. mRNA profiling of activated human T cells cocultured with MSC-sEVs or vehicle control was performed using the QIAGEN Illumina sequencing platform. Pathway networks and biological functions of the differentially expressed genes were analyzed using Ingenuity pathway analysis (IPA)® software, KEGG pathway, GSEA and STRING database. A total of 364 differentially expressed genes were identified in sEV-treated T cells. Canonical pathway analysis highlighted the RhoA signaling pathway. Cellular development, movement, growth and proliferation, cell-to-cell interaction and inflammatory response-related gene expression were altered. KEGG enrichment pathway analysis underscored the apoptosis pathway. GSEA identified enrichment in downregulated genes associated with TNF alpha and interferon gamma response, and upregulated genes related to apoptosis and migration of lymphocytes and T-cell differentiation gene sets. Our findings provide valuable insights into the mechanisms by which MSC-sEVs implement immunomodulatory effects on activated T cells. These findings may contribute to the development of MSC-sEV-based therapies.

Original languageAmerican English
Article number13689
JournalInternational Journal of Molecular Sciences
Volume24
Issue number18
DOIs
StatePublished - 5 Sep 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Ingenuity Pathway Analysis
  • T lymphocytes
  • gene set enrichment analysis
  • mesenchymal stem cells
  • next-generation sequencing
  • small extracellular vesicles

Fingerprint

Dive into the research topics of 'Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Apoptosis, TNF Alpha and Interferon Gamma Response Gene mRNA Expression in T Lymphocytes'. Together they form a unique fingerprint.

Cite this