Abstract
Amniotic fluid stem cells (AFSCs) are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA) of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs) following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain’s circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.
Highlights
Amniotic fluid cells obtained by amniocentesis have routinely been cultured and used for prenatal genetic testing
Amniotic fluid-derived stem cells (AFSCs) have been demonstrated to share some characteristics with MSCs, including differentiation potential and immunophenotypic properties
We detected a high percentage of CXCR4+ cells (17.9%) in AFSCs samples, implying that AFSCs may have superior therapeutic potential compared to bone marrow mesenchymal stem cells (BMMSCs)
Summary
Amniotic fluid cells obtained by amniocentesis have routinely been cultured and used for prenatal genetic testing. Amniotic fluid-derived stem cells (AFSCs) represent ~1% in amniotic fluid cells recovered from second trimester amniocentesis samples, and the fetal origin of these cells has been confirmed by molecular evidence [1]. AFSCs express early embryonic markers that are absent in other adult stem cells, including Oct-4, Nanog and stage-specific embryonic antigen (SSEA-4) [2,3]. These findings suggest that AFSCs represent an early developmental stage that is intermediate to embryonic and adult stem cells in terms of their versatility and that they have unique potential for further applications [3,4]. AFSCs have been shown to stimulate the regeneration of mammary gland [6] and sciatic nerve [7] in animal models
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