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

Stem Cell Research & Therapy

Paula M Alves¹  Maria J Sebastião¹  Margarida Serra¹  Patrícia Gomes-Alves¹  Ramón Menta²  Belén Sanchez²  Itziar Palacios²  Wilfried Dalemans³  Eleuterio Lombardo⁴  Olga DelaRosa⁴ 

[1] Animal Cell Technology Unit, iBET, Instituto de Biologia Experimental e Tecnológica;Coretherapix, S.L.U. (TiGenix Group);TiGenix NV;TiGenix SAU;

关键词: Cardiac stem/progenitor cells;    Allogeneic stem cell therapy;    Tryptophan metabolism;    Immunosuppression;    T lymphocytes;   

DOI  :  10.1186/s13287-018-1010-2

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown