Abstract
Objectives: A low level of placental growth factor (PlGF) expression in placenta is strongly correlated with pregnancy loss, prematurity, fetal growth restriction, and preeclampsia. Pristane-induced lupus in mice model has been widely used to present placental damage and poor pregnancy outcomes. Conditioned media (CM), which is medium for culturing mesenchymal stem cells (MSCs), have grown much attention recently. It has rich amount of growth factors, exosomes, microvesicles, and immunomodulatory molecules. These could become beneficial resources to recover poor placentation.
 Methods: CM taken from the 3rd to 4th passage of the culture were underdone by using explant method of human umbilical cord (hUC). Ninety BALB/c mice were randomly distributed into three groups: Normal, pristane, and pristane + CM group. Mice in normal group were injected with 0.5 ml normal saline and other groups with 0.5 ml pristane. Four weeks later, mice were mated and only pristane + CM group received therapy of CM-MSCs 0.5 ml single dose after pregnancy was confirmed. On day 16, pregnancy was terminated and the placenta was analyzed for PlGF expression using immunoreactive score and statistically tested with analysis of variance.
 Results: The average of PlGF expression in normal, pristane, and pristane + CM group was 9.528, 3.428, and 10.085, respectively. CM have significantly increase PlGF (p<0.01**) and equal to normal (p=0.301).
 Conclusion: CM of hUC-MSCs has shown its therapeutical effect among the low level of PlGF in damaged placenta, and potentially would prevent fetal growth restriction and preeclampsia arose from spiral artery remodeling failure.
Highlights
Placental growth factor (PlGF) is believed as the most important molecules in placenta that supporting proper angiogenesis and good placentation process [1]
Conditioned media (CM) of human umbilical cord (hUC)-mesenchymal stem cells (MSCs) has shown its therapeutical effect among the low level of PlGF in damaged placenta, and potentially would prevent fetal growth restriction and preeclampsia arose from spiral artery remodeling failure
CM of hUC-MSCs were produced in the amount of 360 ml from a single culture process, taken from the 3rd and 4th passages
Summary
Placental growth factor (PlGF) is believed as the most important molecules in placenta that supporting proper angiogenesis and good placentation process [1]. A low level of PlGF will significantly increase the risk of poor pregnancy and provide information to identify highrisk pregnancy before clinical manifestation arise. PlGF expression in placenta after pristane induction has never been reported in any study before. Stem cells have become a trending topic as a new modality in therapy. It has been used in many relevant clinical setting. CM of hUC-MSCs is expected to restore poor placentation process in low PlGF expression setting by increasing PlGF expression in placenta
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