UCLA research may help scientists understand what causes pregnancy complications

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UCLA research may help scientists understand what causes pregnancy complications Researchers identify cells involved in placenta development Dr. Hanna Mikkola and researchers at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have identified a specific type of cell and a related cell communication pathway that are key to the successful growth of a healthy placenta. The findings could greatly bolster our knowledge about the potential causes of complications during pregnancy.

Specifically, the findings could help scientists clarify the particular order in which progenitor cells grow in the placenta, which would allow researchers to track fetal development and identify complications. Progenitor cells are cells that develop into other cells and that initiate growth of the placenta.

The study was led by Mikkola, associate professor of molecular, cell, and developmental biology, and Dr. Masaya Ueno, a UCLA postdoctoral fellow. It was published online by the scientific journal Developmental Cell on Nov. 25 and will appear later in the journal's print edition.

The placenta is the organ that forms inside the uterus during pregnancy and enables oxygen and nutrients to reach the fetus, but little is understood about the biological mechanisms and cellular processes responsible for this interface. Studying mouse models, Mikkola and her colleagues tracked individual cells in the placenta to determine which cells and which cell communication routes, or signaling pathways, were responsible for the healthy development of the placenta.

The UCLA team was the first to identify the cells that form the placenta: Epcamhi labyrinth trophoblast progenitors, or LaTP cells, can become the various cells necessary to form a specific tissue, in this case the placenta. Mikkola and her colleagues also found a signaling pathway that consists of hepatocyte growth factor and its receptor, c-Met. The researchers found that this signaling pathway was required for the placenta to keep making LaTP cells. Production of LaTP cells, in turn, continues the production of the different cells needed to maintain the growth and health of the placenta while the fetus is growing. Placental health enables healthy transmission of oxygen and nutrients through the exchange of blood between the fetus and the mother. In the mice, when c-Met signaling stopped, fetal growth slowed, the liver did not develop fully and it produced fewer blood cells, and the fetus died.

"Identifying this novel c-Met–dependent multipotent labyrinth trophoblast progenitor is a landmark that may help us understand pregnancy complications that are caused by defective placental exchange, such as fetal growth restriction," Mikkola said.

### Mikkola's research was supported by the National Institutes of Health, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, the Japan Society for the Promotion of Science, the American Association of Obstetricians and Gynecologists, the California Institute of Regenerative Medicine, the Jonsson Comprehensive Cancer Center at UCLA, and the Ruth L. Kirschstein National Research Service Award.

The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA's Jonsson Comprehensive Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.

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