Year 1

Prematurity/preterm birth is the leading cause of perinatal morbidity and mortality both in the U.S. and in California. These babies are at increased risk for long-term disabilities, including cerebral palsy, gastrointestinal problems, and vision and hearing loss. Many premature babies also suffer from low birth weight, which not only increases complications in the perinatal period, but also leads to increased cardiovascular disease and diabetes in adulthood. The majority of these perinatal complications result from abnormal development and function of the placenta, a transient organ that forms the interface between mother and baby. Trophoblasts are the primary cells which carry out major placental functions such as establishing blood supply from the mother to the fetus. In this application, we proposed the placenta as a novel target for stem cell therapy and sought to generate human trophoblast stem (TS) cells, which give rise to all subtypes of trophoblasts in the placenta.
During the first year of this grant period, we have focused on characterization of a protein, which is promising as a marker for trophoblast proliferation and regeneration. We have confirmed that this protein, named p63, in fact plays a major role in keeping placenta-derived trophoblast cells regenerating in a culture dish. We have also discovered that this protein is expressed early after induction of human embryonic stem cell differentiation into trophoblast. We are currently testing the effect of up- and down-regulation of this protein in both human placenta-derived and human embryonic stem cell-derived trophoblast. We hope that by modifying this single protein, we will be able to maintain human trophoblast in culture. This would be a major step towards identification and generation of true human trophoblast stem cells.