A Bumpy Road for Stem Cells

By Rhitu Chatterjee
ScienceNOW Daily News
23 October 2006

There's good news and bad news from the world of embryonic stem cell research. A team has successfully treated Parkinson's disease in rats by transplanting nerve cells derived from human embryonic stem cells, but it has also found that these transplanted cells can form tumors in the brain.
Parkinson's disease is caused by the death of dopamine-producing cells in the midbrain. Because dopamine helps neurons communicate, the loss of these cells disrupts motor function in patients. Scientists hope that by replacing these cells, they can cure the disease. Thus far, the best candidate has been embryonic stem cells, which can give rise to any cell type in the body. Experiments with mouse and human embryonic stem cells, however, have successfully turned only about 20% of these cells into dopamine-producing nerve cells in the lab--not enough to treat the disease successfully.

To increase this yield, neurologist Steven Goldman of the University of Rochester Medical Center in New York and his colleagues cultured human embryonic stem cells with growth factors and mature nerve cells known to encourage the development of dopamine-producing neurons in the brain. The result: a whopping 70% to 80% success rate. When the researchers transplanted these mature cells into the brains of six rats treated with a chemical that killed their dopamine neurons, the transplanted cells grew and connected with other nerve cells in the brain. Within 8 weeks, every rat had recovered its lost motor function, the authors reported online yesterday in Nature Medicine.

However, an analysis of the rat brains 10 weeks after transplant revealed that only about one-fifth of the transplanted cells were producing dopamine. And worse yet, the rest had started dividing uncontrollably into benign brain tumors. Previous stem-cell studies have also found tumors, but in those cases the tumors had arisen from immature stem cells. Here, the stem cells had already matured into dopamine-producing cells before transplant, so the authors suspect that the tumors in this study arose from immature--or undifferentiated--neural precursor cells that contaminated the transplant culture. This means that "we've to get rid get these undifferentiated cells before we transplant these neurons," says Goldman.

"The big news here is caution," says stem-cell expert Evan Snyder of the Burnham Institute of Medical Research in San Diego, California. Still, he says that Goldman and colleagues have fine-tuned the process of using embryonic stem cells for treating Parkinson's disease and that further research will eventually find "the recipe to make it perfect."