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Immunomodulatory effects of primed amniotic fluid-derived mesenchymal stem/stromal cells with IFN-γ from unexplained
Seyed Mehdi Hoseini1,2, Ahmad Reza Bahrami2,3, Seyed Mehdi Kalantar4
1Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
The immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) are strongly influenced by IFN-γ priming and may vary depending on their tissue of origin. This study investigates whether the immunoregulatory responses of human amniotic fluid-derived MSCs (hAF-MSCs) to IFN-γ are altered when derived from individuals with unexplained recurrent pregnancy loss (RPL). We analyzed 10 well-characterized hAF-MSC clones, equally divided into non-RPL and RPL groups, to assess IFN-γ-induced expression of immunomodulatory genes. Additionally, we evaluated the paracrine effects of MSC-conditioned medium on T regulatory (Treg) cell induction and macrophage polarization. Significant differences were observed between the two groups in the expression of immunomodulatory markers following IFN-γ priming, as well as in their capacity to induce Treg cells and modulate M1/M2 macrophage polarization. These findings support the hypothesis that dysregulated immune pathways contribute to unexplained RPL by revealing impaired IFN-γ responsiveness in hAF-MSCs from fetuses derived from couples with the history of RPL.
The immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) are strongly influenced by IFN-γ priming and may vary depending on their tissue of origin. This study investigates whether the immunoregulatory responses of human amniotic fluid-derived MSCs (hAF-MSCs) to IFN-γ are altered when derived from individuals with unexplained recurrent pregnancy loss (RPL). We analyzed 10 well-characterized hAF-MSC clones, equally divided into non-RPL and RPL groups, to assess IFN-γ-induced expression of immunomodulatory genes. Additionally, we evaluated the paracrine effects of MSC-conditioned medium on T regulatory (Treg) cell induction and macrophage polarization. Significant differences were observed between the two groups in the expression of immunomodulatory markers following IFN-γ priming, as well as in their capacity to induce Treg cells and modulate M1/M2 macrophage polarization. These findings support the hypothesis that dysregulated immune pathways contribute to unexplained RPL by revealing impaired IFN-γ responsiveness in hAF-MSCs from fetuses derived from couples with the history of RPL.
