Stem cells illuminate early stages of human development

When introduced to the world in 1998, human embryonic stem cells were considered heralds of a new age of transplant medicine. The prospect of an unlimited supply of cells and tissue of all kinds to treat disease captured public imagination and enthusiasm.

But lost in the glitz of the cells’ potential to treat an array of devastating and sometimes fatal diseases was another quality that, when all is said and done, could match even the prospect of remaking transplant technology.

“Much of the excitement surrounding embryonic stem cell research focuses on their potential for transplantation to repair diseased organs,” according to Thaddeus G. Golos, a University of Wisconsin-Madison professor of obstetrics and gynecology. “The cells are also a valuable model for beginning to understand the puzzles of early human development.”

Indeed, a team led by Golos and colleagues at the Wisconsin National Primate Research Center has now taken some of the first critical steps to putting stem cells to use to understand early development and maternal and fetal health. Writing in the December online editions of the journal Endocrinology, the team led by Golos reports the development of a stem cell model that mimics the formation of the placenta during the earliest stages of human development.

The lab feat is important because prior to the advent of human embryonic stem cells, science’s primary window to early development was through studies of mice and other animal models. Human embryonic stem cells and the work of Golos’ team has now brought the very first stages of human development, as an embryo implants itself in the uterus, within reach of science. The work could one day help clinicians better understand and treat diseases of pregnancy such as preeclampsia, a disorder that occurs only during pregnancy and the postpartum period and that, by conservative estimates, kills at least 76,000 women and infants each year.

A key aspect of the work by the Wisconsin team was the creation of embryoid bodies, clumps of cells that arise when undifferentiated stem cells are removed from flat culture plates and grown in a suspended culture of proteins and hormones.

“Embryoid bodies are not embryos, but are spherical structures that form when embryonic stem cell colonies are released from the culture surface and grown in suspension,” Golos explains.

In that environment, the team subsequently observed the development of trophoblast cells from the embryoid bodies. These specialized cells are the building blocks that lead to the formation of the placenta, which orchestrates a maternal environment that protects and nurtures a fetus during pregnancy.

Golos said that when the embryoid bodies were transferred into an artificial matrix that mimics the network of proteins that surrounds all of the cells in our bodies, his group observed a dramatic increase in trophoblasts’ secretion of hormones associated with pregnancy.

“Moreover, the cell outgrowths that we observed from the embryoid bodies resembled aspects of the process by which placenta formation occurs as the embryo implants into the womb,” Golos explains. “The opportunity to model these processes with embryonic stem cells is important because the earliest stages of placental function and how its development is controlled cannot be studied in human embryos or early human pregnancy.”

By using embryonic stem cells to create a window to these very early stages of human development, scientists now can gain access to the cellular and chemical secrets of how such critical features as extraembryonic membranes, especially the placenta, grow and develop during pregnancy.

“These steps are essential for the establishment and maintenance of pregnancy,” says Golos. “The establishment of mammalian pregnancy requires that the early embryo make a timely decision to begin to form the placenta, the first functional fetal organ.”

The big picture, according to Golos, is that a better basic understanding of the events that occur during human pregnancy will ultimately lead to advances in maternal and fetal health. Down the road, such knowledge may lead to fewer birth defects, a lower incidence of miscarriage, and improved health for women and infants.

Co-authors of the new Endocrinology paper include Behzad Gerami-Naini, Oksana V. Dovzhenko, Maureen Durning and Frederick H. Wegner of the Wisconsin National Primate Research Center, and James A. Thomson of the Wisconsin National Primate Research Center and the UW-Madison Medical School’s Department of Anatomy.

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– Terry Devitt 608-262-8282, trdevitt@wisc.edu

The March of Dimes Foundation and the National Institutes of Health supported the work of the Wisconsin team.