Background: Preeclampsia is a common obstetric syndrome affecting women in their first pregnancy and characterized by hypertension and proteinuria, which appears after 20 weeks of gestation. It is characterized by high blood pressure and occasional damage to another organ system most often the liver and kidneys. Currently, the etiology and pathogenesis of this syndrome are not fully understood. Since mesenchymal stem cells/stromal cells (MSCs) are intimately associated with endothelial cells that line vessel walls in the decidua they may play some role in the pathogenesis of this syndrome. In this study, we have partly, unveiled the mechanism of preeclampsia pathogenesis at the stem cells level.
Methods: We have isolated and characterized MSCs from decidua basalis of preeclampsia placenta (PE-DBMSCs) and showed their decreased functionality in terms of proliferation, migration, adhesion and clone formation potential as compared to MSCs isolated from decidua region of normal placentae (DBMSCs). The cells were preconditioned with H2O2 and the functional characteristics were evaluated. Differentially expressed genes were analyzed using mass spectrometry. Immunoblotting confirmed the expression of these proteins.
Results: Pre-conditioning with H2O2 restored the functional outcome of PE-DBMSCs. Mass spectrometry (MS) analysis of differentially expressed proteins revealed HMOX1 as one of the major candidates missing in PE-DBMSCs. HMOX1 inhibition by tin protoporphyrin (SnPP) in normal DBMSCs resulted in a reduction in proliferation, migration, adhesion, and clone formation processes as compared to the untreated controls. mRNA and protein analyses of PE-DBMSCs preconditioned with H2O2 at lower doses showed upregulation of HMOX1 expression.
Conclusions: We hereby show for the first time that loss of function of stem cells/stromal cells isolated from the patients with preeclampsia may contribute towards the disease exacerbation. Our results suggest that HMOX1 may be partially responsible for the loss of functionality in PE-DBMSCs and contribute significantly towards the pathophysiology of preeclampsia. However, further investigation is required to decipher its exact role in the development and onset of the disorder.
Keywords: Decidua basalis mesenchymal stem cells; HMOX1; Preconditioning; Preeclampsia; Tin protoporphyrin; xCELLigence.