IMMUNOLOGICAL PROPERTIES OF CD117+ AMNIOTIC FLUID STEM CELLS OBTAINED DURING DIFFERENT TRIMESTERS OF GESTATION

Le cellule staminali da liquido amniotico sono cellule multipotenti ricavabili attraverso una selezione ed espansione ex-vivo delle cellule esprimenti il CD-117. La dimostrazione della loro capacità di differenziarsi in tutte le linee cellulari ha creato grande interesse su questo potenziale nuovo strumento terapeutico. Tuttavia la loro immunogenicità e le proprietà immunomodulatorie non sono del tutto chiare, e necessitano di essere ben studiate prima della loro eventuale applicabilità clinica. Scopo di questo lavoro è atto quello di analizzare i diversi effetti immunologici tra le cellule stesse ed alcuni immunoeffettori, nei tre trimestri di gravidanza.

Amniotic Fluid Stem (AFS) cells are multipotent stem cells achievable through the positive selection and ex-vivo expansion of CD117 (c-Kit)-expressing cells derived from amniotic fluid. Given the broad differentiation potential toward adipogenic, osteogenic, myogenic, endothelial, neuronal and hepatic lineages, AFS cells have raised great interest as new therapeutic tool. However, their immunogenicity and immunomodulatory properties need to be assessed before clinical use. To this aim, we analyzed the immunological effects resulting from the interaction between AFS cells of different gestational age and a number of immune effector cells (IECs), i.e. T, B and NK cells. Resting 1st trimester-AFS cells showed lower expression of HLA class-I molecules and NK-activating ligands than 2nd and 3rd trimester-AFS cells. This feature was associated to lower sensitivity of 1st trimester-AFS cells to NK cell-mediated lysis. Nevertheless, inflammatory priming of AFS cells by IFN-γ and TNF-α enhanced the resistance of all AFS cell types to NK cell cytotoxicity. AFS cells modulated lymphocyte proliferation in a different manner according to gestational age: 1st trimester-AFS cells significantly inhibited T and NK cell proliferation, while 2nd and 3rd trimester-AFS cells were less efficient. In addition, only inflammatory-primed 2nd trimester-AFS cells could suppress B cell proliferation, which was on the contrary unaffected by the other AFS cells. Indolamine 2,3 dioxygenase (IDO) pathway was not significantly involved in 1st trimester-AFS cells-mediated T cell suppression, while it was the main inhibitory mechanism in 2nd and 3rd trimester-AFS. Overall, this study revealed a number of significant qualitative and quantitative differences among AFS cells of different gestational age in terms of phenotype, immunological functions and immunogenicity, which all have to be taken into consideration in view of AFS cell clinical application.