Endothelial nitric oxide synthase-engineered mesenchymal stromal cells induce anti-inflammation in experimental immune models

Jennifer A. Korchak, Mina Delawary, Peng Huang, Cuiping Zhang, Koji Suda, Abba Chedi Zubair

Research output: Contribution to journalArticlepeer-review

Abstract

Background aims: Mesenchymal stromal cells (MSCs) remain an area of interest in the field of regenerative medicine. Although there is clear evidence of safety, a lack of substantial efficacy has led to many MSC-based clinical trials to stall in phase 1. Therefore, potentiating MSCs with biologically relevant messenger RNA (mRNA) transcripts presents a relatively safe and efficient way to increase functionality. Methods: In this study, human bone marrow-derived MSCs were transfected with endothelial nitric oxide synthase (eNOS) mRNA and evaluated for transfection efficiency and immunosuppressive ability. To assess MSC-eNOS functionality, T-cell proliferation assays and mouse models of experimental autoimmune encephalomyelitis and graft-versus-host disease were used. Results: The authors found that MSC-eNOS retained MSC characteristics and exhibited significantly enhanced immunosuppressive effects compared with naive MSCs in both in vitro and in vivo models. Conclusions: It is feasible to pursue eNOS mRNA transfection to potentiate the immunomodulatory capacity of MSCs for clinical applications in the future.

Original languageEnglish (US)
JournalCytotherapy
DOIs
StateAccepted/In press - 2021

Keywords

  • cell therapy
  • eNOS
  • mesenchymal stromal cells
  • regenerative medicine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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