Amniotic mesenchymal cells from pre-eclamptic placentae maintain immunomodulatory features as healthy controls

Area of Science:

• Immunology
• Obstetrics
• Regenerative Medicine

Background:

• Pre-eclampsia (PE) is a severe pregnancy syndrome with poorly understood mechanisms.
• PE involves immune system alterations, including increased inflammatory cells (Th1/Th17/APC) and decreased regulatory cells (Th2/Treg).
• Amniotic membrane cells' role in PE is unclear, despite observed inflammatory infiltrates.

Purpose of the Study:

• To investigate if the immunomodulatory properties of human amniotic mesenchymal stromal cells (hAMSC) are altered in pre-eclamptic pregnancies.
• To compare the in vitro immunomodulatory functions of hAMSC from pre-eclamptic (PE-hAMSC) versus normal (N-hAMSC) pregnancies.

Main Methods:

• Comprehensive phenotypic study of hAMSC isolated from PE and normal pregnancies.
• In vitro assessment of immunomodulatory properties of PE-hAMSC and N-hAMSC.
• Analysis of T-cell proliferation, cytokine polarization, regulatory T-cell induction, and dendritic cell differentiation.

Main Results:

• PE-hAMSC effectively inhibit CD4/CD8 T-cell proliferation and suppress Th1/Th2/Th17 polarization.
• PE-hAMSC promote regulatory T-cell (Treg) induction and block dendritic cell differentiation, shifting them to M2 cells.
• PE-hAMSC exhibit enhanced Treg induction and greater interferon-γ suppression compared to N-hAMSC, linked to increased TGF-β1 and PD-L1/L2 expression.

Conclusions:

• Human amniotic mesenchymal stromal cells (hAMSC) from pre-eclamptic pregnancies do not have impaired immunomodulatory functions.
• These cells do not contribute to pre-eclampsia pathogenesis.
• hAMSC may play a role in mitigating the inflammatory environment characteristic of pre-eclampsia.