A New Twist for Embryonic Stem Cells in the Heart
By M. William Lensch, Ph.D.

The research article by Diego Fraidenraich and colleagues [1] from Memorial Sloan-Kettering Cancer Center and the Weill Medical College of Cornell University presents a fascinating series of experimental results using mouse embryonic stem cells to correct a syndrome of congenital heart defects in fetal mice. The initial heart defects they describe are very complex and result from the loss of a group of genes known as Id's (for Inhibitor of Differentiation). This genetic defect impacts several structures in the developing heart, resulting in death in the developing mice before they can be born.

This paper puts a few new twists on things that differ from the goal of using embryonic stem cells to craft new cardiac tissue to repair damaged hearts.   First, the heart defects that the authors address occur in mice developing within the uterus; most concepts of stem cell-derived cardiac therapy are envisioned for cases of heart tissue damage in adult, heart attack sufferers. Also, while the authors show that the defects can be corrected by introducing normal embryonic stem cells into the embryo soon after fertilization (and before any heart structures are known to form) they also show that the new, healthy stem cells need not be present within the heart at all. Instead, they show that placing normal stem cells in the mother can also significantly correct much of the heart damage.

They go on to show that this works because the normal stem cells injected into the mother produce a specific hormone (called IGF-1) that is able to enter the mother's bloodstream and eventually make its way into the developing mice in the uterus where it can prevent much (but not all) of their heart damage. The authors then show that simply injecting the hormone (and no stem cells at all) has the same effect, thus proving the point that the stem cells probably work by secreting IGF-1. Finally, they show that one other gene is involved (called Wnt5a) and that in combination with IGF-1, completely corrected the heart defects.

What's the bottom line here? Two things come to mind. (1) By using embryonic stem cells to study development, some important things have been learned about congenital heart defects, things that one day may lead to improved therapies. (2) Therapies with embryonic stem cells may come from not only using them to directly replace damaged/diseased tissue, but also as micro-factories to produce hormones or other important factors that can protect tissues from disease or perhaps repair the damage once it does occur. While we are hopeful that both might be possible in the days to come, only time will tell if these therapeutic goals will come to pass. However, one thing is certain, that research with embryonic stem cells is producing some exciting, unexpected, and very positive results in our efforts to both understand complex aspects of biology and fight disease.  

 M. William Lensch, Ph.D. is a Leukemia & Lymphoma Society Fellow at Children's Hospital Boston.

[1] Science , 306:247-252, 2004

Updated: February 2, 2005