Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1593-1605 |
| Number of pages | 13 |
| Journal | Journal of Cellular and Molecular Medicine |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 1 2015 |
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Keywords
- Cell culture
- Cloning
- Immunosuppression
- Lymphocytes
- Pluripotent stem cells
- T cells
ASJC Scopus subject areas
- Cell Biology
- Molecular Medicine
Cite this
Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1. / 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.
In: Journal of Cellular and Molecular Medicine, Vol. 19, No. 7, 01.07.2015, p. 1593-1605.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1
AU - Romani, Rita
AU - Pirisinu, Irene
AU - Calvitti, Mario
AU - Pallotta, Maria Teresa
AU - Gargaro, Marco
AU - Bistoni, Giovanni
AU - Vacca, Carmine
AU - Di Michele, Alessandro
AU - Orabona, Ciriana
AU - Rosati, Jessica
AU - Pirro, Matteo
AU - Giovagnoli, Stefano
AU - Matino, Davide
AU - Prontera, Paolo
AU - Rosi, Gabriella
AU - Grohmann, Ursula
AU - Talesa, Vincenzo N.
AU - Donti, Emilio
AU - Puccetti, Paolo
AU - Fallarino, Francesca
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Cell culture
KW - Cloning
KW - Immunosuppression
KW - Lymphocytes
KW - Pluripotent stem cells
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84933048675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84933048675&partnerID=8YFLogxK
U2 - 10.1111/jcmm.12534
DO - 10.1111/jcmm.12534
M3 - Article
AN - SCOPUS:84933048675
VL - 19
SP - 1593
EP - 1605
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 7
ER -