Investigating of Therapotic Effects of Mesenchymal Stem Cell Derived Exosomes in L-NAME Rat Model of Preeclampsia

Preeclampsia is defined as a disease characterized by the onset of hypertension and proteinuria in a normotensive woman after 20 weeks of gestation. Although the etiology of the disease is not known, it is a complex syndrome which is one of the leading causes of maternal and fetal mortality and morbidity. Therefore, the identification of molecules responsible for the process is very important. Exosomes already present as natural carriers, their biodistribution and stability in plasma, and their availability from each cell make them a suitable candidate for therapeutic applications. The aim of this study was to evaluate the therapeutic effects of mesenchymal stem cells (MSCs) on biochemical, molecular and behavioral experiments in early and late preeclampsia model induced by L-NAME in rats. Pregnant rats (n = 72) were divided into two main groups as cesarean section (n = 36) and delivery group (n = 36). Each group was divided into 6 subgroups as Early Onset Preeclampsia, Late Preeclampsia, Exosomes, Early Preeclampsia + Exosomes, Late Preeclampsia and Exosomes. L-NAME was treated to pregnant rats with in drinking water. The rats in the treatment group were given intraperitoneal exosomes (600 µl/kg). Systolic blood pressure was measured on days G0, G12 and G19. Our cesarean groups were compared in terms of placenta, fetus weight and numbers. Open area, nowel object recognition and Barnes Labyrinth tests were performed on the 30th and 90th days in order to examine the cognitive memory after termination of pregnancy in 1 mother and a male and a female offsping.At the end of the experiment, mRNA fold changes in placentas were determined by RT-PCR. Some proteins in the serum were tested with ELISA. H & E staining was performed to examine the placental histopathology. In conclusion, this study suggested that BM-MSC-Ex- based treatment normalizes abnormal blood pressure, proteinuria and the expression of Flt-1 and Eng in serum in a L-NAME-induced PE rat model and improves edema, dilatation and hemosiderin granule accumulation in the placenta. These data indicate that BM-MSC-Ex can improve learning disability and cognitive memory in preeclamptic mothers and their offspring, and may be an alternative approach for the treatment of PE. Although this study emphasizes the beneficial effect of BM-MSC-Ex in a PE rat model, its application in clinical therapy requires more research and approval. In addition, more detailed molecular genetic studies are needed to fully elucidate the role of BM-MSC-Ex in the preeclampsia pathways.