Stem Cells Used to Model Infant Birth Defect

One of the powerful uses of stem cells is their ability to model diseases. One recent report shows how stem cells can provide such a use.

Do you remember those strawberry-like birthmarks you have? They’re called hemangiomas. For the most part they are quite harmless. However, a stark minority of hemangiomas (~10%) can cause trouble if they occur within particular tissues. Hemangiomas consist of knots of blood vessels and if they form in the eyes, they can produce vision trouble, and if they form in lungs, they can cause circulation defects in the lungs.  Worse still, hemangiomas can continue growing and become tumors.

Traditionally, treatment of damaging hemangiomas has been with steroid drugs. There are problems with such treatments though. Steroids have many undesirable side effects, and they don’t always work. Even more troubling is the fact that the means by which steroids work are a complete mystery.

Now, workers at Children’s Hospital Boston recently shown that hemangiomas that form during development come from stem cells. Additionally, by growing these stem cells in the laboratory, scientists have been able to use them to understand how steroids treat hemangiomas (New England Journal of Medicine, March 18).

Hemangiomas are tangles of blood vessels that originate from specialized stem cells called hemangioma stem cells.  These cells can overgrow and produce little knobs of tissue.  Steroids work by shutting down the ability of hemangioma stem cells to grow.  In order to grow, hemangioma stem cells make a growth factor called vascular endothelial growth factor-A (VEGF-A).  This self-made growth factor increases the growth of the hemangioma stem cells, and steroids shut down the production of VEGF-A, thus inhibiting their growth.

Why is this exciting?  It turns out that VEGF-A is rather well understood, and there are other tools for inhibiting VEGF-A signaling.  This means that much safer drugs are available to treat hemangiomas.  Furthermore, not all hemangiomas respond to steroids (~30%).  This work suggests that hemangioma stem cells that form the hemangiomas may harbor mutations that causes them to overgrow and form knots of blood vessels.  Some of these mutant stem cells respond to steroids and some do not.  Some of the screening methods applied in this study may tell pathologists if steroid treatment will help or not.

By using stem cells from the tumor and manipulating them in the laboratory, scientists were able to learn basic things about common tumors and often manifest themselves as birthmarks.  This is hopefully only one of many different kinds of diseases that will be modeled through experiments on stem cells.