S1P promotes migration, differentiation and immune regulatory activity in amniotic-fluid–derived stem cells

Romani, R. and Manni, G. and Donati, C. and Pirisinu, I. and Bernacchioni, C. and Gargaro, M. and Pirro, M. and Calvitti, M. and Bagaglia, F. and Sahebkar, A. and Clerici, G. and Matino, D. and Pomili, G. and Di Renzo, G. C. and Talesa, V. N. and Puccetti, P. and Fallarino, F. (2018) S1P promotes migration, differentiation and immune regulatory activity in amniotic-fluid–derived stem cells. European Journal of Pharmacology, 833. pp. 173-182.

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Stem cells have high potential for cell therapy in regenerative medicine. We previously isolated stem cell types from human amniotic fluid, derived from prenatal amniocentesis. One type, characterized by a fast doubling time, was designated as fast human amniotic stem cells (fHASCs). These cells exhibited high differentiation potential and immunoregulatory properties. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that influences stem-cell pluripotency, differentiation, mobility, and regulates immune functions. In this study, we investigated the influence of S1P on fHASC migration, proliferation, differentiation and immune regulatory functions. We found that fHASC stimulation with S1P potentiated their migratory and proliferative activity in vitro. Notably, short fHASC exposure to S1P enhanced their differentiation towards multiple lineages, including adipocytes, osteocytes and endothelial cells, an effect that was associated with downregulation of the main transcription factors involved in the maintenance of a stem-cell undifferentiated state. A specific crosstalk between S1P and tumor growth factor β1 (TGF-β1) has recently been demonstrated. We found that fHASC exposure to S1P in combination with TGF-β1 promoted the expression of the immune regulatory pathway of indoleamine 2,3-dioxygenase 1 (IDO1). In addition, human peripheral blood mononuclear cells, co-cultured with fHASCs treated with S1P and TGF-β1, expanded regulatory T-cells, via a mechanism requiring IDO1. Overall, this study demonstrates that S1P potentiates several properties in fHASCs, an effect that may be critical for exploiting the therapeutic potential of fHASCs and might explain the specific effects of S1P on stem cells during pregnancy. © 2018

Item Type: Article
Additional Information: Cited By :1 Export Date: 16 February 2020 CODEN: EJPHA Correspondence Address: Fallarino, F.; Department of Experimental Medicine, University of PerugiaItaly; email: francesca.fallarino@unipg.it
Uncontrolled Keywords: 3 dioxygenase Amniotic Fluid Stem Cells Indoleamine 2 Sphingosine-1-phosphate TGF-β1 dioxygenase indoleamine 2,3 dioxygenase 1 sphingosine 1 phosphate transcription factor transforming growth factor beta1 unclassified drug indoleamine 2,3 dioxygenase indoleamine 2,3-dioxygenase 1, human lysophospholipid sphingosine sphingosine 1-phosphate TGFB1 protein, human adipocyte adult amniotic fluid stem cell Article cell differentiation cell lineage cell migration coculture controlled study down regulation endothelium cell exposure female flow cytometry human human cell immunoregulation in vitro study osteocyte peripheral blood mononuclear cell pregnancy priority journal protein expression protein protein interaction regulatory T lymphocyte amnion fluid analogs and derivatives cell culture cell motion cell proliferation cytology drug effect immunology metabolism mononuclear cell physiology pluripotent stem cell signal transduction Amniotic Fluid Cell Movement Cells, Cultured Humans Indoleamine-Pyrrole 2,3,-Dioxygenase Leukocytes, Mononuclear Lysophospholipids Pluripotent Stem Cells T-Lymphocytes, Regulatory
Subjects: WQ Obstetrics
QU Biochemistry
QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 06 May 2020 12:47
Last Modified: 06 May 2020 12:47
URI: http://eprints.mums.ac.ir/id/eprint/17494

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