| Kali Prasad |
Posted
on 03-May-01 11:29 PM
SOURCE: CHRONICLE OF HIGHER EDUCATION
How to Make a Kidney, an Ear, or Even a Heart
By LILA GUTERMAN
A disembodied nose lives in the middle of a biology lab. The experiment may sound like a scene from Woody Allen's Sleeper, but it's actually state-of-the-art research in the young field of tissue engineering.
Scientists have also created a mouse with tissue shaped like a human ear sprouting from its back. In hospitals, doctors are using commercially produced, lab-grown skin to repair diabetic foot ulcers. And in one operation, a disfigured boy received tissue-engineered cartilage to form a new chest.
Researchers have even bigger plans for the future. Some hope to grow new heart tissue in the lab, while others work toward replacement livers and kidneys. Still others dream of repairing damaged spinal cords.
But the scientists and engineers striving to create such artificial organs haven't reached a consensus on the best types of cells to use to seed the new tissue. Many pin their hopes on the remarkable abilities of stem cells that can be taken from human embryos or adults. But the use of embryonic cells is embroiled in legal and ethical controversy, while stem cells that come from adults are rare and may be less versatile.
Now, a surprising discovery is buoying the hopes of researchers frustrated with the problems and controversies of stem cells. A team from the University of Massachusetts Medical School, in Worcester, led by Charles A. Vacanti, has discovered a type of cell, hiding in material previously thought to be debris, that may outperform all other cell types. Researchers imagine that these cells might even allow them to teach the body to heal itself.
The new cells are tiny, found in every tissue the researchers have examined, and can survive freezing or near-boiling temperatures. Other scientists hesitate to endorse the discovery completely at this early stage, but they are brimming with excitement. "It's not just an incremental increase in our knowledge, it's a quantum leap," says Doros Platika, president and chief executive officer of Curis, a biotechnology company in Cambridge, Mass. "If it can be reproduced and pans out, it would potentially be Nobel Prize-winning work."
The new cells are creating such buzz in part because tissue engineers see a desperate problem in need of a solution. On average, there are 50,000 more patients needing organs every year than there are donations.
To move beyond the early, attention-getting successes at building tissue in the lab, researchers must deal with such fundamental issues as creating tissues that will last for years in the body and finding the best scaffolding materials on which new organs can grow. One key to success lies in the starting point. Ideally, scientists would begin with totipotent cells, so named because they have the potential to become any type of mature tissue. The cells could become ligament, lung, or liver.
Embryonic stem cells are such cells. They come from aborted fetuses or extra embryos left over from in vitro fertilization procedures. They multiply well in the lab and can be coaxed into creating nearly any type of cell. But ethical and political concerns make their use practically untenable for researchers financed by federal grants.
Stem cells found in adults share the excellent growth abilities of embryonic cells without the ethical problems, but researchers think they are more limited in their potential to create different tissues. These stem cells are rare and have only been found in a few tissues, including blood and bone marrow.
Last month, scientists from the University of California at Los Angeles reported in the journal Tissue Engineering that they had uncovered a plentiful source of the adult stem cells: fat. The U.C.L.A. team found that the stem cells could develop into at least four different types of tissue: fat, bone, cartilage, and muscle. But researchers are still searching for progenitor cells that could grow into the many other body parts needed to replace diseased or damaged tissue.
That's where the new cells may come in. "We believe that there is in every tissue in the body a very, very immature, very small, very inactive -- so it doesn't require much oxygen to survive -- adult progenitor cell," says Dr. Vacanti, chairman of the anesthesiology department and head of the tissue-engineering center at UMass. "When the tissue is injured, it's activated, it multiplies, and it's supposed to repair the injury."
In March, he and his colleagues announced in the Journal of Cellular Biochemistry that they may have found those cells. Working with spinal-cord tissue from rats, the UMass researchers used tiny filters to remove all the garden-variety cells, leaving only diminutive bits and pieces of material. "What we observed was typically described as debris," Dr. Vacanti says. "But the debris was very round." Something so round was not likely to be just cellular litter, the researchers reasoned, and they tried growing the material as though it were cells. Sure enough, "the debris seemed to multiply well. After it multiplied, it would make multicellular clumps and then individual cells would break off and start to mature," he says.
"It sounds ridiculously simple," says Lawrence J. Bonassar, an assistant professor at the UMass tissue-engineering center and one of the paper's authors. But he thinks other scientists have missed the tiny cells because "it doesn't really make sense that cells should be able to be that small." Each cell, he thinks, is little more than a nucleus, a few mitochondria for energy, and a membrane. They are only 3 to 5 microns across, so that more than a million of them would fit in an average-sized raindrop. Other mammalian cells tend to be around 10 times larger.
When the researchers began to look in other tissues, they found similar small cells. They've now discovered them in 20 different types of tissue in rats, as well as in several sheep and human tissues. The researchers stop short of calling them stem cells because, at present, their role remains unclear. Instead the team uses the term "sporelike" cells because they seem to start from a dormant stage only to burst into life, much like a plant or bacterial spore might. In each case, the sporelike cells can give rise to normal, mature cells of the tissue from which they were originally isolated.
"What impressed us and I've gotten a kick out of ... [is that] we found you can freeze the cells with no protection. You thaw them out weeks or months later, and they start multiplying and differentiating again," says Dr. Vacanti. "Everything else is dead. It's just amazing.
"We haven't heated them to boiling, but we've come close. The cells will survive it, [while] everything else will be denatured and dead." Such extreme environments would kill any other mammalian cell.
Dr. Vacanti says this hardiness may be key to the cells' role as "Mother Nature's repair cells." Conditions that would injure the rest of the tissue leave the sporelike cells unaffected and might trigger them to multiply and replace damaged tissue. But the UMass team has not yet shown that the cells function that way in the body.
The hardiness also makes the cells very attractive for tissue engineering. Many organs, such as the brain, liver, kidney, and lung, have been difficult for tissue engineers to work with because their cells don't survive the lack of oxygen during transplantation. But the researchers think that if they implant these tiny spore cells into a body, the cells will withstand the lag time while the body is generating new blood vessels.
The researchers have found that spore cells from the liver and lung grow into healthy-looking liver and lung tissue when implanted under the skin of mice. "In the lung, we also did a study where we cut out part of [a mouse's] lung and replaced it with spore cells on a polymer scaffold," says Mr. Bonassar. "We got tissue that looked like lung tissue." He says they don't yet know whether the new tissue functions like a healthy lung.
Dr. Vacanti says that he has been surprised at other scientists' positive reaction to his work, since he has claimed to have discovered a new and potentially incredibly useful cell type that other researchers had been discarding as debris. "I suspect a certain number of people think we're nuts," he says.
Michael V. Sefton, director of the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, wouldn't go quite that far, but he is skeptical. "My reaction is that it's too good to be true," he says. "It doesn't fit with things we're used to thinking about. But that doesn't mean it's wrong."
Julia M. Polak, a professor of pathology and head of the tissue-engineering center at Imperial College of Science, Technology, and Medicine, in London, says, "It's fantastic, but it's early days. Other people will have to confirm their finding."
While they wait for others to verify the UMass results, several scientists have begun fantasizing about using the sporelike cells in their research. "If this stuff works, I'd be a user of the cells," says Mr. Sefton. "I think these sporelike cells would be terrific and answer numerous prayers to get around ethical limitations of [embryonic] stem cells or difficulties of isolating [adult stem] cells."
Dr. Platika, of Curis, says that the cells' robustness should be useful because tissue-engineered products made from them will be easy to store. But he has loftier goals in mind: "If we learn how to activate these spores within the body, we could get the body to regenerate and repair itself," he says. "There's the potential to be an internal fountain of youth."
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Section: Research & Publishing
Page: A19
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