10 February 2019
The capacity of key stem cells to respond to oxidative stress, an accumulation of oxygen metabolism by-products, is reduced in preeclampsia. This ﬁnding could lead to the development of new treatments for diseases associated with oxidative stress, such as Alzheimer’s disease, atherosclerosis and hypertension.
Preeclampsia is a pregnancy complication that can cause hypertension and impair liver and kidney function. It is thought to aﬀect 5 to 10% of all pregnancies, and can be life threatening if left untreated.
Researchers in Australia and Saudi Arabia recovered mesenchymal stem cells (MSCs) from the maternal part of the placenta of preeclamptic women and from women whose pregnancies were healthy. MSCs are adult stem cells that can diﬀerentiate into cells found in skeletal tissues. They found that the MSCs from preeclamptic women had reduced expression of the gene ALDH.
MSCs normally express high levels of ALDH, responsible for encoding the enzyme aldehyde dehydrogenase, which protects cells from oxidative stress. MSCs have successfully been used to reduce oxidative stress in several diseases.
The researchers suspected that the defects in stem cells from preeclamptic patients might result from increased oxidative damage, causing the cells to die or reducing their ability to support the neighbouring muscle and endothelium cells.
To test this, the team inactivated ALDH in healthy stem cell cultures and then challenged the cells with hydrogen peroxide, which causes oxidative stress. The engineered cells were more sensitive to hydrogen peroxide than normal cells, conﬁrming the importance of aldehyde dehydrogenase in protecting stem cells. The engineered stem cells may prove an eﬀective model for studying these conditions and developing new treatments.
One approach would be to stimulate ALDH in the defective cells. The team evaluated three known ALDH activators. They found that two increased the expression of aldehyde dehydrogenase in preeclamptic stem cells, reducing the damage caused by hydrogen peroxide. “That was an exciting moment, because it gave us hope that a therapy targeting this pathway could be a viable treatment,” says Mohamed Abumaree of King Saud Bin Abdulaziz University for Health Services, who took part in the study.
“Restoring the resistance to oxidative stress may reduce the maternal symptoms of preeclampsia, allowing the pregnancy to continue and reducing the need for premature delivery,” he continues, adding that “searching for new strategies to reduce oxidative stress may be eﬀective in preventing atherosclerosis and thereby cardiovascular disease.”
- Kusuma, G. D., Abumaree, M. H., Perkins, A. V., Brennecke, S. P., & Kalionis, B. Reduced aldehyde dehydrogenase expression in preeclamptic decidual mesenchymal stem/stromal cells is restored by aldehyde dehydrogenase agonists. Scientific Reports 7, 42397 (2017) | article