Emerging Therapeutic Potential of Mesenchymal Stem/Stromal Cells in Preeclampsia

Abstract

Purpose of review: Preeclampsia is a dangerous pregnancy condition affecting both the mother and offspring. It is a multifactorial disease with poorly understood pathogenesis, lacking effective treatments. Maternal immune response, inflammation and oxidative stress leading to endothelial dysfunction, are the most prominent pathogenic processes implicated in preeclampsia development. Here, we give a detailed overview of the therapeutic applications and mechanisms of mesenchymal stem/stromal cells (MSCs) as a potential new treatment for preeclampsia.Recent findings: MSCs have gained growing attention due to low immunogenicity, easy cultivation, and expansion in vitro. Accumulating evidence now suggests that MSCs act primarily through their secretomes facilitating paracrine signalling that leads to potent immunomodulatory, pro-angiogenic and regenerative therapeutic effects. Summary:MSCs have been studied in different animal models of preeclampsia demonstrating promising result, which support further investigations into the therapeutic effects and mechanisms of MSC-based therapies in preeclampsia, steering these therapies into clinical trials.

Mechanisms of Key Innate Immune Cells in Early- and Late-Onset Preeclampsia

“…Furthermore, MSCs have also been shown to have a key proangiogenic role in pregnancy (70). In preeclampsia, the function of MSCs is likely impaired due to exposure to increased numbers of reactive oxygen species (ROS) (70,71).…”

“…Simultaneously, MSCs stimulate the shift of T-helper cells from a Th1 to Th2 phenotype by promoting IL-4 production and inhibiting IFN-γ production, thus heightening maternal immunological tolerance of the fetus. Furthermore, MSCs have also been shown to have a key pro-angiogenic role in pregnancy ( 70 ). In preeclampsia, the function of MSCs is likely impaired due to exposure to increased numbers of reactive oxygen species (ROS) ( 70 , 71 ).…”

“…Furthermore, MSCs have also been shown to have a key pro-angiogenic role in pregnancy ( 70 ). In preeclampsia, the function of MSCs is likely impaired due to exposure to increased numbers of reactive oxygen species (ROS) ( 70 , 71 ). The presence of aldehyde dehydrogenases (ALDH) during normal pregnancy assists in detoxification from ROS, thus providing a degree of protection against oxidative damage ( 71 ).…”

“…Increased attention has been directed toward investigating the role of MSCs and their immunomodulatory capacity during pregnancy and its complications. As their potential therapeutic role in preeclampsia has been discussed elsewhere ( 70 , 162 , 163 ), here we discuss their contribution to irregular innate immune system signaling in preeclampsia. MSCs are found in many tissues, such as bone marrow, and adipose, decidual and fetal tissue ( 164 – 166 ).…”

Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular Vesicles Toward Mainstream Medicine for Lung Injuries Associated With SARS-CoV-2 Infections

“…Since the key for the treatment of SARS-CoV-2 infection lies in the management of the cytokine storm in the lungs, MSCs are well-suited considering their main mechanism of action is through their immunomodulatory and anti-inflammatory properties (Fatima et al, 2017). The safety profile and efficacy of MSCs are well-established based on the results from a number of completed clinical studies investigating the therapeutic potential of these therapies in lung diseases such as ARDS (Matthay et al, 2019; and bronchopulmonary dysplasia (Namba, 2019), cardiovascular diseases (Kim et al, 2015;Suvakov et al, 2020), diabetes (Thakkar et al, 2015;Cho et al, 2018), and spinal cord injury (Xu and Yang, 2019).…”