Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1

Rita Romani, Irene Pirisinu, Mario Calvitti, Maria Teresa Pallotta, Marco Gargaro, Giovanni Bistoni, Carmine Vacca, Alessandro Di Michele, Ciriana Orabona, Jessica Rosati, Matteo Pirro, Stefano Giovagnoli, Davide Matino, Paolo Prontera, Gabriella Rosi, Ursula Grohmann, Vincenzo N. Talesa, Emilio Donti, Paolo Puccetti, Francesca Fallarino

Research output: Contribution to journalArticlepeer-review


Although human amniotic fluid does contain different populations of foetal-derived stem cells, scanty information is available on the stemness and the potential immunomodulatory activity of in vitro expanded, amniotic fluid stem cells. By means of a methodology unrequiring immune selection, we isolated and characterized different stem cell types from second-trimester human amniotic fluid samples (human amniotic fluid stem cells, HASCs). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASCs. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASCs exhibited regulatory properties when treated with interferon (IFN)-γ, including induction of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). On coculture with human peripheral blood mononuclear cells, IFN-γ-treated fHASCs caused significantly decreased T-cell proliferation and increased frequency in CD4+ CD25+ FOXP3+ regulatory T cells. Both effects required an intact IDO1 function and were cell contact-independent. An unprecedented finding in our study was that purified vesicles from IFN-γ-treated fHASCs abundantly expressed the functional IDO1 protein, and those vesicles were endowed with an fHASC-like regulatory function. In vivo, fHASCs were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD4+ CD25+ Foxp3+ T cells in graft-draining lymph nodes from recipient mice. Thus fHASCs, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo.

Original languageEnglish
Pages (from-to)1593-1605
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Issue number7
Publication statusPublished - Jul 1 2015


  • Cell culture
  • Cloning
  • Immunosuppression
  • Lymphocytes
  • Pluripotent stem cells
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine


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