TROPHOBLAST STEM CELLS
Lay Review
Stem Cell Biology Graduate Course, Fall 2006

Prepared by: Mary Gergis and Sharon Soh
Teaching Assistant: Helen Liou

Stem cell research is growing everyday with the discovery of stem cells just about everywhere in the body and even in the developing embryo.  After an egg becomes fertilized, the embryo divides several times to form a ball-like cluster of cells, called the blastocyst (1, Fig. 1).  Four to five days after fertilization, the blastocyst is made of a cluster of cells on the inside of the blactocyst, the inner cell mass (ICM) and the trophoectoderm, which is surrounding the ICM (1,2) (Fig. 1).  Embryonic stem cells (ESC) are derived from the ICM and go on to form all three germ layers of the developing fetus.  Trophoblast stem cells (TS cells) come from trophoectoderm (1).

Trophoblast stem cells (TS cells) have been gaining interest in the scientific community for several reasons.  Firstly, TS cells form several types of cells that mediate implantation of the embryo as well as physiological adaptations during pregnancy, such as regulation of maternal blood flow, and form layers of the placenta (2).  The cells derived from the TS cells assist in adapting maternal physiology during pregnancy, synthesizing angiogenic factors, vasodilators, and anticoagulants which help to promote local blood flow to the implantation site (3).  Also, cells derived from the TS cells produce hormones and cytokines to direct maternal blood flow to the implantation site as well as directing the production of progesterone in the ovary to aid in implantation (2).  In addition, these signals stimulate the production of milk by the mammary glands, lactogenesis (2).  Studying TS cells and the cells they give rise to is important to understanding embryonic development and the factors that maintain embryonic growth and survival (4). 

In addition to aiding in implantation, TS cells give rise to cells such as, the spongiotrophoblast cell (SpT), which constitutes the middle layer of the placenta (3, Fig.1).  The placenta has many important functions in the developing embryo.  It supports the embryo with its branched villi that provide a large surface area for nutrient, waste and gas exchange (3).  The placenta is thought of an organ with multiple functions that are important in development.  

Trophoblast stem cells are vital to establishing implantation and placental development.  It has been shown that defects in placental development lead to pregnancies that are at risk for miscarriage and intrauterine growth retardation, and are associated with preeclampsia, a leading cause of maternal death and premature birth (5).   The goal of studying TS cells can lead to solutions to a variety of fertility problems, such as embryos that fail to implant or embryos that form placental defects that are detrimental to the embryo.  Also, studying TS cells and the cells they derive can lead to treatments of birth defects in embryos while they are still in a developmental stage and that can be altered to promote a healthy pregnancy.  

References

1. Rossant, Janet. Stem Cells from the Mammalian Blastocyst. Stem Cells 2001; 19;447-82.

2. Cross JC. How to Make a Placenta: Mechanisms of Trophoblast Cell Differentiation in Mice. Placenta 2005,A:S3-9.

3. Simmons DG, Cross JC. Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Dev Biol 2005;284:12-24.

4. Takahashi Y, Carpino N, Cross JC et al. SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation. EMBO J 2003;22:372-84.

5. Gultice AD, Selesniemi K L, Brown TL. Hypoxia Inhibits differentiation of lineage-specific Rcho-1 trophoblast giant cells. Biol Reprod 2006;74:1041-50.