Grant Project Title:
Establishment and characterization of miscarriage-specific human trophoblast stem cells
750,000 to 1,000,000 miscarriages happen in the United States annually. For couples who experience pregnancy loss, the cause is usually cytogenetic in 60% of cases, such as trisomy and monosomy. However, the cause of the remaining euploid miscarriages is usually not found. Therefore, there is a significant need for more studies to investigate new causes of human pregnancy loss, especially recurrent miscarriages, where 50% of couples will not find a cause. To elucidate the molecular mechanisms of miscarriages in humans, new tools are necessary to study these events as up until now; one significant barrier is the limited amount of tissue, mainly chorionic villi, available for analysis. Prior studies on early human placentation have primarily relied on transformed trophoblast cell lines or primary human trophoblast cells purified from the early placenta, which cannot be propagated. Therefore, a proliferating primary trophoblast cell culture system to study human miscarriage is an essential technical advancement to overcome these past research barriers. Recently, researchers have established control human trophoblast stem (TS) cell lines from first-trimester chorionic villi from normal pregnancies and human blastocysts from IVF. Therefore, our project aims to establish human TS cells from first-trimester miscarriage chorionic villi as a new tool to elucidate the pathophysiology of unexplained first-trimester miscarriages and ultimately find new causes of recurrent miscarriages.
This ASRM Research Institute grant has been instrumental in providing me with the essential funds to carry out the necessary pilot experiments required to establish the feasibility of this high-risk, high-reward research project. Furthermore, the data generated from this grant has provided the crucial scientific support and feasibility data required to submit a competitive R01 grant and to help me towards my long-term career goal to be an independent physician-scientist. It is hard to express in a few words how grateful I am to ASRM Research institute for providing this grant to me as it allows me to ‘stay in the research game’ and one day translate my bench research to help couples with recurrent miscarriages.
Winifred Mak, MD, PhD
Associate Professor, UT Health Sciences at San Antonio and Dell Medical School (UT Austin)