"A more realistic light" on embryonic stem cell research

"Some folks are portraying this as imminently useful and it's not."

"This [experiment] shows the incredible potential of the field, but it also sheds a more realistic light on the near-future potential."

These are comments from scientists in Nature.com and the Globe and Mail of Canada that sheds "light" on the Parkinson's treatment experiment with embryonic stem cells that has been covered by JivinJehosaphat , MaryMeetsDolly, and SK at the LTI blog.

The Canton Repository mentions that this is similar to another (little publicized) report published October 11, 2006 (abstract only - does not mention the tumors) in the journal, Stem Cells, which showed similar results. In contrast, the Geron corporation (part of the Wicell/ACT/Geron stem cell connection that I wrote about here and here)representatives tell us that they have (unpublished) results using stem cells in spinal cord injury that do not cause tumors.

None of the articles on Goldman or Isacson (that I've read) mentions that adult stem cells have produced relief in human patients, without tumors, in spinal cord injuries, Parkinson's disease and Lou Gerig's disease.


News@nature.com covers the report originally published online in Nature Medicine (this is the abstract, the full article is available by subscription only) and explains the technique used to encourage the development of the dopamine-producine cells:

[Stephen Goldman, Ph.D.] and his team took human fetal midbrain tissues, in which dopamine cells are made, and extracted glial cells, whose normal role is to support and maintain the growth of neurons. They then cultured stem cells in this glia-rich environment.

"What we were really trying to do was to mimic the environment of the developing brain to increase the efficiency of dopamine-neuron generation, but also to bias the cells towards generating the type of dopamine neurons that we wanted," says Goldman.

The technique worked. When the new dopamine neurons were transplanted into the brains of rats with the symptoms of Parkinson's disease, the animals recovered almost entirely. "The positive results were really remarkably strong," Goldman says. "The animals exhibited almost a complete restoration of normal function."

But there could be alarming side effects. Each stem-cell transplant also contained cells that had failed to become neurons, and which remained undifferentiated. These cells keep dividing, and can turn into tumours, says Goldman. (The rats in the study were killed before any such tumours developed.)

The human embryonic stem cells were first grown in cultures of human fetal nerve tissues (harvested from human infants who had been aborted at 11 to 22 weeks of age), that had themselves been manipulated ("telomorase-immortalized") and selected for producing the "glial cells" that support the developemnt of the specific brain cells that produce dopamine. We knew from past experiments that transplants of fetal tissues cause tumors in the brain of experimental subjects.

The Globe and Mail's review, "A Sobering Set-back in Stem Cell Research," explains the experiment very clearly:

Twenty years worth of studies have tried treating Parkinson's with dopamine-cell transplants, in rodents, primates and people. In the 1990s, after a Swedish study found some benefit to patients who received dopamine-cell transplants from aborted fetal tissue, large human trials began in both Canada and the United States.

"These failed," Dr. Goldman said. "It made things worse; patients suffered movement abnormalities." In part, he explained, this was because the transplants contained all sorts of cells. Less than 10 per cent of the cells, and in some cases, less than 1 per cent, produced dopamine.

For this reason, Dr. Goldman, a neurologist and chief of cell and gene therapy at the University of Rochester, and many others, considered embryonic stem cells a possible source of growing only the cells that would be needed and they were right. But no one had been able to grow enough for a transplant.

In this experiment, however, Dr. Goldman and his team overcame the volume problem by tricking the embryonic stem cells into behaving like they were growing in the developing brain.

To do this, they harvested glial, or brain-support cells, from the precise brain region of an aborted fetus that would, at 11 to 22 weeks gestation, trigger the development of the dopamine neurons needed.

The researchers then used a retrovirus as a courier to deliver into the DNA of these cells a gene, known as telomerase, which would immortalize them. This way, Dr. Goldman explained, the support cells would continue to grow endlessly and continuously give off the chemical cues to keep stem cells maturing into dopamine cells.

The dopamine cells had first been grown from the limited number of human embryonic stem-cell lines that U.S. President George W. Bush made available to government-funded researchers in 2000.

Culturing the immortalized glial cells alongside the stem-cell derived dopamine neurons -- although not touching each other -- resulted in a growth of dopamine cells three to 10 times what is normally seen.

But Dr. Bhatia, who read the report, said this step might have contributed to the uncontrolled growth of the cells.

Comments on the experiment and where it went wrong focus on the known risks of transplanting fetal and embryonic stem cells and the need to isolate only those stem cells which are destined to become the exact dopamine-producing cells that were the desired results.

I keep wondering why the scientists don't approach the question from the other side: turn adult cells from the patient into precursors of the dopamine producing cells or activate the patient's own stem cells.