Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1.
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.
['Romani|Rita|R|', 'Pirisinu|Irene|I|', 'Calvitti|Mario|M|', 'Pallotta|Maria Teresa|MT|', 'Gargaro|Marco|M|', 'Bistoni|Giovanni|G|', 'Vacca|Carmine|C|', 'Di Michele|Alessandro|A|', 'Orabona|Ciriana|C|', 'Rosati|Jessica|J|', 'Pirro|Matteo|M|', 'Giovagnoli|Stefano|S|', 'Matino|Davide|D|', 'Prontera|Paolo|P|', 'Rosi|Gabriella|G|', 'Grohmann|Ursula|U|', 'Talesa|Vincenzo N|VN|', 'Donti|Emilio|E|', 'Puccetti|Paolo|P|', 'Fallarino|Francesca|F|']
D000328:Adult D064591:Allografts D000653:Amniotic Fluid D000818:Animals D015415:Biomarkers D002450:Cell Communication D002454:Cell Differentiation D049109:Cell Proliferation D002469:Cell Separation D048430:Cell Shape D002999:Clone Cells D058732:Embryoid Bodies D006085:Graft Survival D006801:Humans D056747:Immunomodulation D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase D007371:Interferon-gamma D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D016513:Mice, SCID D010641:Phenotype D039904:Pluripotent Stem Cells D013234:Stem Cells D050378:T-Lymphocytes, Regulatory
T cells cell culture cloning immunosuppression lymphocytes pluripotent stem cells