More MS news articles for July 2001

Stem-cell research provides scientists with new hope

They claim cures might be found for debilitating diseases.

Monday, July 16, 2001
By Faye Flam

As President Bush agonizes over whether to allow taxpayer-funded research on stem cells from human embryos, neurologist Jeffrey Rothstein is injecting these cells into mice to see whether they can slow the relentless nerve degeneration that comes with amyotrophic lateral sclerosis, or Lou Gehrig's disease.

Rothstein and his colleagues at Johns Hopkins University, who are privately funded, are transplanting so-called embryonic stem cells into mice with a condition similar to ALS, which often starts with weakness in the arms or legs and eventually robs the patient of the ability to walk, talk, and, in the end, breathe.

Other scientists around the country, most of them testing the controversial embryonic cells in mice or rats, are looking at their potential for some of the most devastating conditions - brain diseases such as Parkinson's and Alzheimer's, spinal-cord injuries, and the irreparable scarring caused by heart attacks.

The research is so new and the power of these cells is so little understood that scientists don't know whether stem cells will revolutionize medicine. But they will never know if they aren't allowed to study them, they argue.

Adding fuel to the debate over using embryos is new evidence that stem cells taken from adult donors show some of the same promise.

Currently, research is allowed on embryo stem cells only if private money is used, but that restriction has made such research impossible for many scientists, who can't gather sufficient funds. Wise Young, director of the W.M. Keck Center for Collaborative Neuroscience at Rutgers University in Piscataway, Middlesex County, said stem cells represent one of the most promising avenues of research for spinal-cord injury. If Bush decided to allow federal funding for work with these cells, "that would stimulate a flurry of research in my lab and other labs."

"Stem cells are a very major issue to the spinal-cord injury community," Young said. "Why should they be penalized for the religious beliefs of a few?"

The promise of these embryonic stem cells comes from their seemingly magical ability to transform themselves into any of the more than 100 kinds of tissue that make up the human body.

First isolated and grown in the lab in 1998, the cells have spawned visions of new spinal-cord tissue for paralysis patients, pancreatic cells to cure diabetes, heart cells that would repair the scarring of a heart attack, reinforced bone for osteoporosis, or new skin for burn victims.

Currently, some embryonic stem cells are taken from aborted fetuses, isolated, and then allowed to multiply in culture dishes. Others come from the microscopic embryos that are routinely created and either frozen or destroyed in fertility clinics. Such embryos develop for just a handful of days and, never progressing beyond the stage of a cluster of "undifferentiated" cells, have yet to specialize as different types of tissues.

Lobbying against using embryonic stem cells are the Catholic Church and others who believe that life begins at conception with a fertilized egg.

These groups argue that there is no need to exploit human embryos, citing reports of stem cells being obtained from bone marrow and other sources in adults, either live donors or cadavers.

Scientists are not yet ready to say whether adult cells would work as well as embryonic cells. Not enough research has been done, they say, and almost all of it has been in animals.

So far, embryonic stem cells have been turned into more than 100 different types of cells, far more than adult stem cells. Also, embryonic stem cells can reproduce indefinitely in the lab; adult stem cells eventually die.

Peter Donovan, who conducts stem-cell research at Thomas Jefferson University Hospital, said it is possible that the medical community may decide never to use embryonic stem cells, opting instead for the adult cells. But to learn how to use any of these stem cells, he said, "we'll need to study both types."

John McDonald at Washington University, St. Louis, has been studying the embryonic stem cells as a treatment for paralysis. In 1999, he injected the severed spinal cords of paralyzed rats with rat stem cells.

While the rats didn't recover completely, they gained function - some degree of mobility, sensitivity, bladder control - the kinds of things that can be important to people with spinal-cord injuries. And such success may not ever come from the adult stem cells, he argued.

He has since begun using human embryonic stem cells in rats and mice, with similar results.

McDonald just started testing this technique, using stem cells from pig embryos, on people paralyzed by spinal-cord injuries. There are no results yet from the one patient who has received treatment.

Meanwhile, Ira Black of the New Jersey College of Medicine and Dentistry, working with former Hahnemann University professor Darwin Prockop, who is now at Tulane in New Orleans, is concentrating on adult stem cells. They obtained such cells from bone marrow taken from student volunteers.

Black and Prockop knew that stem cells from bone marrow could become bone, cartilage, fat and muscle. But last year they proved they could also transform it into brain tissue. That led them to inject the stem cells into rats that had been given a form of Parkinson's disease. The cells took up residence in the brain, where new brain tissue was needed, Prockop said, and the animals showed some improvement.

Prockop said the bone marrow stem cells are now being tested as a treatment for a genetic abnormality called brittle bone disease, which causes people to fracture at the slightest impact. In animals, the cells seem to migrate to the deficient skeleton. Human trials are expected soon.

Some opponents of embryo research point out that some patients are now getting stem cells from umbilical-cord blood, taken when babies are born. But so far such cells have only produced blood cells, limiting their use to blood diseases such as leukemia.

The first study to compare the benefits of embryonic stem cells with adult cells is the ALS work on mice being done at Johns Hopkins.

Early results, in which they transferred mouse stem cells to mice, showed "dramatic" improvement for the mice that got embryonic stem cells, Rothstein said, but not for the ones that got cells from other sources. The Hopkins group has since begun transplanting human stem cells of different types into the mice. The results, Rothstein said, are confidential, having been sent to a journal but not yet published.

Rothstein hopes the mice experiments will answer some questions beyond ALS.

"We're one small disease, but it has a pretty big impact," said Rothstein. Their research could point to similar treatments for multiple sclerosis, Parkinson's disease, paralysis, or Alzheimer's.

Even if the adult stem cells prove superior in the ALS trial, Rothstein remains convinced that embryonic stem cells hold tremendous promise. He said that any decision to continue the federal funding ban would be "a bad mistake."

Donovan of Jefferson argues that embryonic cells hold keys to our understanding of the way life works. Virtually every cell in the body carries the person's complete genetic code, and yet the cells take myriad forms and functions. Some mysterious mechanism seems to tell them whether to become bone, muscle, organ, nerves, or blood.

Stem cells may hold the secret behind the cells' ability to find their identities, and, combined with the knowledge from the human genome project, could give scientists a huge insight into the way life is put together.

Such an understanding would be critical, Donovan said, for making the stem cells truly useful in medicine.

Still, he cautioned that impressive new ideas - such as gene therapy - don't always live up to the public's hopes.

"We don't want to promise too much too soon."