Studies Revive Debate Over What Adult Stem Cells Can Do

Several recent scientific studies suggest that adult stem cells can produce a range of tissues, reviving prospects that many benefits of embryonic stem cells could be realized without the accompanying moral and regulatory pitfalls.

The studies are preliminary and have not been validated by other laboratories. But they give a boost to a field that has been largely dismissed by many leading researchers as a medical dead end.

Unlike embryonic stem cells, which have enormous medical promise because they can grow into every tissue type in the body, adult stem cells are narrowly focused on regenerating a single type of tissue.

Scientists have theorized it might be possible to turn back their developmental clocks and retrain them to behave more like embryonic cells. The new results lend some credence to that view.

At a teaching hospital affiliated with Tufts University School of Medicine, stem cells extracted from human bone marrow helped rebuild heart muscle and blood vessels in rats. At AntiCancer Inc., a biotech company in San Diego, researchers induced stem cells from mouse hair follicles to become neurons. At the University of Indiana, scientists transformed stem cells from mouse bone marrow into nerve cells that facilitate hearing.

But some proponents of embryonic stem cells say they are unconvinced their colleagues have unlocked any new abilities of adult stem cells, partly because past experiments have failed to stand the test of time.

“Extraordinary claims require extraordinary evidence,” said Larry Goldstein, who studies embryonic stem cells at the UC San Diego School of Medicine and the Howard Hughes Medical Institute.

Adult stem cells are alluring to medical research because they are easy to collect and offer the possibility of treating patients with their own cells, avoiding problems of tissue rejection.

They also raise no ethical dilemmas because they can be created without destroying any embryos. That trait has endeared them to social conservatives, who promote the latest research as a justification for restricting the creation of new embryonic stem cell lines.

The human body contains a variety of adult stem cells, typically found in places that require frequent regeneration. For instance, hematopoietic stem cells in bone marrow produce red blood cells, platelets, lymphocytes and other kinds of blood cells.

But the cells are limited. In their natural state they can’t transform into the full range of tissue types that embryonic stem cells can. Scientists call this phenomenon plasticity.

The ultimate goal of stem cell research is to harness their tissue-making abilities to grow replacement parts for patients. Doctors could treat patients with juvenile diabetes, for example, by growing new islet cells capable of making insulin.

Adult stem cell research looked promising several years ago, especially after Dr. Catherine Verfaillie and a team of scientists at the University of Minnesota reported in a 2002 issue of the journal Nature that mesenchymal cells, which are found in bone marrow, could be persuaded to produce bone, fat, muscle, blood, liver, intestinal and neuron-like cells.

But the studies by Verfaillie and others were attacked by some prominent stem cell researchers.

Among them was Dr. Irving Weissman, director of Stanford University’s stem cell institute, who failed in attempts to repeat the early studies. Instead, he published several papers debunking claims of adult stem cell plasticity.

Stem cell samples taken from bone marrow might have been contaminated with other cells that grew into the muscle or brain cells that were observed, he said. The researchers also might have witnessed a rare phenomenon in which bone marrow cells fuse with other kinds of cells. Or, the stem cells produced chemical markers indicative of other kinds of tissue without making the tissue itself.

“We’ve shown by now that blood-forming stem cells don’t change their fate to become neurons, they don’t change their fate to become cardiomyocites, they don’t change their fate to become skeletal muscle, and they don’t change their fate to become liver cells,” Weissman said.

Proponents of adult stem cells agree that some of the early claims saddled the field with a credibility problem.

“A lot of the initial studies may have been touted to be more positive than they were,” said Verfaillie, director of the Stem Cell Institute at the University of Minnesota. “That obviously makes the whole field have a blemish on it.”

The new studies have been conducted with the past critiques in mind.

Their tentative indications demonstrate a larger point: adult stem cells are not as rigid as once thought.

“Even though we don’t have all the i’s dotted and ts crossed, it’s kind of hard for me to believe that all of us see things that don’t exist,” Verfaillie said.

To begin with, researchers have started to make headway in reproducing the broad strokes of past studies.

Alan Mackay-Sim, deputy director of the Institute for Cell and Molecular Therapies at Griffith University in Brisbane, Australia, studies adult stem cells from the odor-sensing region of the human nose, and he suspected the stem cells would be able to produce neurons through a relatively straightforward regeneration mechanism.

What startled him was the discovery of a smattering of liver and heart muscle cells. He realized he had reproduced some aspects of an earlier paper that focused on stem cells from mouse brains.

“Effectively what we’re saying is we’ve repeated it,” said Mackay-Sim, who published his findings last month in the journal Developmental Dynamics. “It’s really exciting to see that.”

A group of researchers in Boston has made significant progress in corroborating some of the results of Verfaillie’s 2002 article.

Dr. Douglas Losordo, chief of cardiovascular research at St. Elizabeth’s Medical Center, the Tufts teaching hospital, and his team started with samples of bone marrow and eliminated any cell that already had started to make proteins, indicating that it had set off on a preordained destiny. The remaining cells were isolated in laboratory dishes, where most of them died.

Those that survived were grown in culture. Losordo hoped they would multiply without differentiating into specific kinds of tissue, he said.

Altogether, they isolated nine lines of adult stem cells capable of producing a wide range of tissues. Other labs are working to reproduce the study, which was published in February in the Journal of Clinical Investigation.

“Our interest in this is therapeutic, so if we’re the only lab that can do it, it’s useless,” Losordo said. “We want to see it turn into a process that can be replicated on a large scale.”

Scientists don’t fully understand the chemical reactions behind their observations. One theory is that the cells may have forgotten what they were programmed to make and regressed to an earlier developmental state, when their options were more plentiful.

But after eliminating all known cell types, Losordo thinks he may have stumbled upon a different kind of adult stem cell that behaves like an embryonic stem cell. The cells may in fact be remnants of early development that were never channeled to a particular destiny.

“The idea that you have stem cells residing in most organs as a leftover from embryogenesis opens up a whole new vista,” said Joel Glover, a physiology professor at the University of Oslo in Norway who turned stem cells from human blood into neurons by injecting them into chicken embryos. “People weren’t thinking in those lines before.”

Skeptics are withholding judgment. Some acknowledge they haven’t had time to read the latest papers offering evidence of adult stem cell plasticity.

“I’m turning a blind eye to all of it,” said Goldstein, of UC San Diego. “I figure if something really good happens, I’ll hear about it and go read about it.”