Journal
STEM CELL RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13287-018-1010-2
Keywords
Cardiac stem; progenitor cells; Allogeneic stem cell therapy; Tryptophan metabolism; Immunosuppression; T lymphocytes
Funding
- project NETDIAMOND - FEEI - Lisboa2020 [SAICTPAC/0047/2015, FCT/POCI-01-0145-FEDER-016385]
- iNOVA4Health - FCT/Ministerio da Educacao e Ciencia [UID/Multi/04462/2013]
- FEDER under the PT2020 Partnership Agreement
- FCT fellowship [SFRH/BD/52339/2013]
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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.
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