BIOLOGY Lots of hPMCs are needed in the endometrium during conception as they play a vital role in assisting the rapid growth of the placenta. With a depleted number of these stem cells, as found in women suffering from recurrent miscarriages, there are not enough cells being produced in the placenta to allow it to grow adequately and this also affects and interrupts the interaction between the lining of the uterus and the placenta which can lead to miscarriage [5]. Overall, a lack of these stem cells means that the endometrium has worse conditions to support the embryo and there is also extra stress placed on the specialised decidual cells (which could breakdown the lining and also cause miscarriage) [6]. Using information from these trials, scientists are now researching ways of preventing recurrent miscarriages through increasing the number of hPMCs in the endometrium by either physically inserting more in, or encouraging the differentiation of more hPMCs. There is a trial currently happening that is investigating the use of Sitagliptin, a drug used for diabetes, in preventing miscarriage. When an enzyme, called DPP4, is too active, it can stop the stem cells from being directed to the endometrium which could explain why there is a lack of hPMCs in the endometrium in certain women. The sitagliptin drug acts as a DPP4 inhibitor and therefore allows the stem cells to reach the endometrium as normal and perhaps prevent miscarriage [7]. An initial trial for this drug went ahead at the start of 2020 where 38 women suffering from recurrent miscarriages were given the sitagliptin drug or a placebo. The results showed that the number of stem cells in the endometrium increased by 68% after taking the sitagliptin whilst there was no increase with the placebo [7]. The number of stressed decidual cells also decreased by 50%. A further clinical trial will be happening for this drug over the course of the next year and will hopefully be able to prevent thousands of recurrent miscarriages.
Results from the sitagliptin trial showing that there was a bigger change in the CFU count when using the Sitagliptin compared to barely any change when using the placebo. A CFU count shows the ability of the stem cells to proliferate and differentiate in this sample.
Overall, this information from the Warwick study has provided crucial information about how miscarriages are caused and has therefore prompted the research and further trials of treatments that will help to prevent recurrent miscarriages.
16
