Amniotic Fluid Stem Cells with Low gamma-Interferon Response Showed Behavioral Improvement in Parkinsonism Rat Model

作者:Chang Yu Jen; Ho Tsung Yen; Wu Mei Ling; Hwang Shiaw Min; Chiou Tzyy Wen*; Tsai Ming Song
来源:PLos One, 2013, 8(9): e76118.
DOI:10.1371/journal.pone.0076118

摘要

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 gamma-IFN. We found that stimulation of AFSCs with gamma-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 gamma-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 gamma-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%26apos;s circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to gamma-IFN implies that AFSCs might have immune-tolerance in gamma-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.