Human cardiac stem cells inhibit lymphocyte proliferation through paracrine mechanisms that correlate with indoleamine 2,3-dioxygenase induction and activity

Maria J. Sebastião, Ramón Menta, Margarida Serra, Itziar Palacios, Paula M. Alves, Belén Sanchez, Olga Delarosa, Wilfried Dalemans, Eleuterio Lombardo, Patrícia Gomes-Alves

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5 Citations (Scopus)

Abstract

Transplantation of allogeneic human cardiac/stem progenitor cells (hCSCs) is currently being tested in several phase I/II clinical trials as a novel and promising therapy for restoration of myocardial tissue function in acute myocardial infarction (AMI) patients. Previous findings demonstrate that these cells have an immune suppressive profile interacting with different populations from the immune system, resulting in overall attenuation of myocardial inflammation. However, transplanted hCSCs are still recognized and cleared from the injured site, impairing long retention times in the tissue that could translate into a higher clinical benefit. In this work, through modeling allogeneic hCSC/T lymphocyte interaction in vitro by direct contact, transwell inserts, and hCSC conditioned medium, our results demonstrate that hCSCs exert an immune-suppressive effect on T lymphocyte proliferation not only through the previously described cell contact-dependent programmed cell death-1 (PD1)/programmed death ligand-1 (PDL-1) axis but also through a paracrine mechanism associated with indoleamine 2,3-dioxygenase (IDO) enzyme-mediated tryptophan metabolism. Such findings constitute a step forward in better understanding the mechanisms of action of transplanted hCSCs in allogeneic settings.

Original languageEnglish
Article number290
JournalStem Cell Research and Therapy
Volume9
Issue number1
DOIs
Publication statusPublished - 25 Oct 2018

Keywords

  • Allogeneic stem cell therapy
  • Cardiac stem/progenitor cells
  • Immunosuppression
  • T lymphocytes
  • Tryptophan metabolism

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