Amniotic fluid cells are the heterogeneous cell population of exfoliated fetal and amniotic cells, in 2003, Prusa et al. reported the discovery of OCT-4 positive cells in amniotic fluid, which is a pluripotent characteristics. The potency of human amniotic stem cells seems to be between pluripotent embryonic and adult stem cells (Cananzi M. et al. 2009). We isolated two types of stem cells from human amniotic fluid (HASCs), which differ in morphology, doubling times, CD117, SSEA-3 and KLF4 expression. HASCs express markers associated with a pluripotent undifferentiated state, and generate all of three primary germ layers, yet will not form tumors upon implantation in vivo. In addition, HASCs possess potent immunomodulatory properties that depend on the expression of indoleamine 2,3 dioxygenase (IDO), an enzyme that catalyzes the degradation of the essential amino acid L-tryptophan to produce catabolites called kinurenine. That HASCs express high levels of IDO, especially upon treatment with pro-inflammatory stimuli, such as INF-g, TGF-b and S1P. Based on this results the HASCs could act on the proliferation and survival of peripheral T cells, promoting organ-antigen specific tolerance. In order to evaluate the immunoregolatory proprietes of the HASC we choose animal model of skin allograft trasplantion. Our results demonstrate that HASC are powerful effectors of the tolerogenic response and are able to prevent rejection of skin graft through IDO dependent mechanism.
Pluripotent stem cells from human amniotic fluidand their immunomodulatory properties
ROMANI, Rita;FALLARINO, Francesca;CALVITTI, Mario;DONTI, Emilio;PUCCETTI, Paolo
2012
Abstract
Amniotic fluid cells are the heterogeneous cell population of exfoliated fetal and amniotic cells, in 2003, Prusa et al. reported the discovery of OCT-4 positive cells in amniotic fluid, which is a pluripotent characteristics. The potency of human amniotic stem cells seems to be between pluripotent embryonic and adult stem cells (Cananzi M. et al. 2009). We isolated two types of stem cells from human amniotic fluid (HASCs), which differ in morphology, doubling times, CD117, SSEA-3 and KLF4 expression. HASCs express markers associated with a pluripotent undifferentiated state, and generate all of three primary germ layers, yet will not form tumors upon implantation in vivo. In addition, HASCs possess potent immunomodulatory properties that depend on the expression of indoleamine 2,3 dioxygenase (IDO), an enzyme that catalyzes the degradation of the essential amino acid L-tryptophan to produce catabolites called kinurenine. That HASCs express high levels of IDO, especially upon treatment with pro-inflammatory stimuli, such as INF-g, TGF-b and S1P. Based on this results the HASCs could act on the proliferation and survival of peripheral T cells, promoting organ-antigen specific tolerance. In order to evaluate the immunoregolatory proprietes of the HASC we choose animal model of skin allograft trasplantion. Our results demonstrate that HASC are powerful effectors of the tolerogenic response and are able to prevent rejection of skin graft through IDO dependent mechanism.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
