Open AccessStem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3‐dioxygenase1
Author(s) -
Romani Rita,
Pirisinu Irene,
Calvitti Mario,
Pallotta Maria Teresa,
Gargaro Marco,
Bistoni Giovanni,
Vacca Carmine,
Di Michele Alessandro,
Orabona Ciriana,
Rosati Jessica,
Pirro Matteo,
Giovagnoli Stefano,
Matino Davide,
Prontera Paolo,
Rosi Gabriella,
Grohmann Ursula,
Talesa Vincenzo N.,
Donti Emilio,
Puccetti Paolo,
Fallarino Francesca
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12534
Subject(s) - amniotic epithelial cells , amniotic fluid , stem cell , biology , microbiology and biotechnology , foxp3 , immunology , transplantation , indoleamine 2,3 dioxygenase , amniotic stem cells , peripheral blood mononuclear cell , in vitro , immune system , adult stem cell , fetus , medicine , endothelial stem cell , biochemistry , pregnancy , tryptophan , genetics , amino acid
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, HASC s). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASC s. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASC s exhibited regulatory properties when treated with interferon ( IFN )‐γ, including induction of the immunomodulatory enzyme indoleamine 2,3‐dioxygenase 1 ( IDO 1). On coculture with human peripheral blood mononuclear cells, IFN ‐γ–treated fHASC s caused significantly decreased T‐cell proliferation and increased frequency in CD 4 + CD 25 + FOXP 3 + regulatory T cells. Both effects required an intact IDO 1 function and were cell contact‐independent. An unprecedented finding in our study was that purified vesicles from IFN ‐γ–treated fHASC s abundantly expressed the functional IDO 1 protein, and those vesicles were endowed with an fHASC ‐like regulatory function. In vivo , fHASC s were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD 4 + CD 25 + Foxp3 + T cells in graft‐draining lymph nodes from recipient mice. Thus fHASC s, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo .