Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3‐dioxygenase1
| Autor: | Francesca Fallarino, Maria Teresa Pallotta, Alessandro Di Michele, Paolo Prontera, Rita Romani, Davide Matino, Irene Pirisinu, Mario Calvitti, Vincenzo Nicola Talesa, Ciriana Orabona, Gabriella Rosi, Jessica Rosati, Stefano Giovagnoli, Carmine Vacca, Paolo Puccetti, Matteo Pirro, Ursula Grohmann, Marco Gargaro, Giovanni Bistoni, Emilio Donti |
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| Rok vydání: | 2015 |
| Předmět: |
lymphocytes
Adult Pluripotent Stem Cells Amniotic fluid Cellular differentiation cloning T cells Cell Communication Cell Separation Mice SCID Embryoid body Biology T-Lymphocytes Regulatory Immunomodulation Interferon-gamma Animals Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Induced pluripotent stem cell Cell Shape Embryoid Bodies Cell Proliferation cell culture Mice Inbred BALB C immunosuppression immunosuppression lymphocytes Stem Cells cell culture pluripotent stem cells immunosuppression lymphocytes cloning T cells Graft Survival Cell Differentiation Amniotic stem cells Original Articles Cell Biology Allografts Amniotic Fluid Clone Cells Cell biology Mice Inbred C57BL Phenotype Cell culture Amniotic epithelial cells Molecular Medicine Stem cell Biomarkers |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.12534 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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