Pluripotent stem cells from human amniotic fluid and their immunomodulatory properties

Foetal cells present in human amniotic fluid (AF) have been used for many years for prenatal cytogenetic diagnosis and only recently a lot of reports suggest that these cells might have additional benefits. Infact, in addition to committed and differentiated cells, AF have been found to contain stem cell subpopulations at least of two types: amniotic fluid mesenchymal stem cells (AFMSC) and amniotic fluid stem cells (AFSCs) (1, 2). AF-derived stem cells (AFSC) have same functions of mesenchymal stem cells (MSCs), but in addition, exhibit a potent expansion capacity and plasticity. So, human AF seem to be a new source of stem cells without any ethical concerns associated with human embryonic stem cells (ESCs) research or with problems associated with MSCs, like invasive procedure of bone marrow drawing, and the differentiation potential that decreases significantly with age(3). They can be used as primary in vitro material for research purpose with no need for transformation or immortalization (1,2). AFSCs are a novel type of stem cells sharing features common to both embryonic and adult stem cells, including phenotypic markers (2). They are able to generate all of the three primary germ layers, even if are not tumorogenic in vivo. Moreover, the AFMSCs have been described to possess immunosuppressive properties, and have the ability to produce Indoleamine 2,3-dioxygenase (IDO, EC1.13.11.42) after exposure to INF-, but at very low levels compared to the placental tissues(4). IDO is an intracellular enzyme containing a heme group that catalyzes the initial limiting reaction of tryptophan degradation by the "kynurenine pathway" (5). It is expressed in a wide variety of human tissues as well as macrophages and dendritic cells, and is induced in various inflammatory conditions by IFN-γ and other pro-inflammatory cytokines; IDO can be considered an important effector system in the regulation of innate and adaptive immune response. Although it represents only one of several ways to induce tolerance, the immunosuppressive pathway of tryptophan catabolism has been shown to contribute to an effective control of immunity (5). Kim et al. (6) demonstrated that the lipid mediator Sphingosine-1-phosphate (S1P) is present in human amniotic fluid, and that it acts on the S1P-specific receptors (S1P1, S1P2, and S1P3) expressed on human amnion-derived WISH cells. S1P is a bioactive sphingolipid metabolite that has been implicated in fundamental biological processes mainly through binding to its specific receptors S1P1-5 in many cell systems (7). Recent literature highlights the role of S1P in the regulation of proliferation, survival, differentiation and migration of several adult and embryonic stem cells (8, 9).