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Stem Cell Research

Cutting Edge Research in Chicago

By ARICKA FLOWERS

"This could be used to help arthritis patients, like those with rheumatoid arthritis or osteoarthritis, as well as people with other joint problems. They could be readily treated with regenerated tissue from adult stem cells."
Imagine a world where there's no Alzheimer's disease. No Parkinson's disease. A world where families are spared the grief of idly standing by as a loved one slips away into their own world of darkness, never to be reached again. A world where diabetes is not controlled-it's cured. Sound too good to be true? Maybe not.

Stem cell researchers say studies are beginning to indicate that a number of diseases could be cured or at least greatly alleviated if regenerated cells are transplanted into an ailing patient. "We have used adult stem cells to regenerate an articular condyle, the knob end of the joint that helps you move and bend," says Dr. Jeremy Mao, director of the Tissue Engineering Laboratory at the University of Illinois at Chicago and associate professor of Bioengineering Orthodontics and Anatomy Cell Biology. "This could be used to help arthritis patients, like those with rheumatoid arthritis or osteoarthritis, as well as people with other joint problems. They could be readily treated with regenerated tissue from adult stem cells."

In other words, the arthritis sufferer could have new cartilage and bone implanted into the area that is causing them pain. Since arthritis is defined as a breakdown of cartilage and bone in a joint, the patient would essentially be healed.

"This is what is called regenerative medicine," explains Mao. "If you have a bad motor in your car, you take it out and put a new one in. The same thing would apply for a bad knee. The ideal approach would be to take stem cells from John Smith with a bad knee and use the cells to regenerate a new knee for John Smith. Currently, surgeons use metallic materials, a patient's own cartilage plugs, or cadaver or animal materials to replace defective body parts. There are several pitfalls associated with these materials like wear and tear, potential pathogen transfer, or the body could simply reject the implant. But one of the biggest problems is that all of these materials have a lifespan. They stop working as well and wear out in about 10 or 15 years."

"The ultimate goal is that a regenerated tissue could integrate with your own biological structure," Mao continues. "It's like when you have a cut on your finger. The new tissue integrates completely with the rest of your hand. Right now it's like robbing Peter to pay Paul when you go into the hip for something that you need to fix in your knee. Instead of using drugs or something that will only improve the conditions, you can totally heal an injury with stem cell regenerated tissue. There will be no pathogen transmission because the regenerated tissue is from your own body and you wouldn't reject it because the structure is grown from your own cells."

Unfortunately, adult stem cells so far have not been proven to be successful in the case of curing certain diseases affecting the liver, kidney and other areas in the body made up of complex tissue.

"The challenging parts of the body to regenerate are internal organs such as the liver and kidney. This is where embryonic stem cells are likely needed," explains Mao, who works solely with adult stem cells.

Unfortunately, adult stem cells so far have not been proven to be successful in the case of curing certain diseases affecting the liver, kidney and other areas in the body made up of complex tissue.
So, what's the big difference between embryonic and adult stem cells?

Simply put, embryonic stem cells come from embryos. They are derived from embryos that were fertilized in a clinic and are at their earliest stage of formation, usually only four or five days old. The cells are removed from the blastocyst, the technical name for an embryo at this point of maturity, and can be used to create stem cell lines that can be grown indefinitely in a lab.

Adult stem cells, on the other hand, originate from adult tissue or organs. The main purpose of adult stem cells is to repair or sustain adult tissues.

Scientists say these differences play a large role in the medicinal capabilities of the two types of stem cells.

"I think it's over-optimistic to say that adult stem cells could work as well as embryonic stem cells in terms of regenerating tissue," says Dr. Janet Rowley, scientist member of President Bush's Council on Bioethics and University of Chicago professor of medicine. "In a number of different areas adult stem cells cannot really develop into the variety of tissue types and cell functions that embryonic stem cells can. Another issue is the renewal capacity of adult stem cells. There is the thought that stem cells have a certain number of divisions before they will become quiescent and die. And if you're starting to work with a cell that has already completed half of its divisions, then it only has half of its lifetime left; and therefore it will not be as effective for as long of a time."

The reason why adult stem cells seem to lack the capacity to develop into a myriad of tissue and organs can also be attributed to their age.

"Embryonic stem cells have only developed one or two times since the beginning of their life, so they have a great amount of development potential," explains Rowley. "The nucleus has not been programmed to work in a specific way like a muscle, cartilage, bone marrow or neurological cell. Because of that they have the possibility to become all types of tissue cells. That is not the case for adult stem cells that have been programmed, in a way, to work like the tissue from where they came."

Scientists say this is why embryonic stem cell research is essential to regenerative medicine. But in 2001, the stem cell research community was dealt a huge blow when President Bush announced strict guidelines surrounding government funding for such work. The president's policy only allowed the U.S Department of Health and Human Service's National Institutes of Health to fund research on 64 established embryonic stem cell lines. That number would later whittle down to 17 NIH-approved stem cell lines. The number decreased because of the president's demands that the approved stem cells be collected from embryos at fertility clinics that would have otherwise been discarded by August 9, 2001. Any other embryonic stem cell research conducted in the U.S. would have to be privately funded.

Researchers say the president's stronghold on the NIH's purse strings is creating an environment that is making embryonic stem cell research increasingly difficult.

"We are working on a variety of stem cell lines and our need to study other lines is becoming progressively larger, especially those derived from somatic cell nuclear transfer (therapeutic cloning)," says Dr. John Kessler, chairman of Neurology at Northwestern University's Medical School. "The president's policies, if implemented, would actually make this a criminal activity. We are using three embryonic stem cell lines in the lab right now, but we have a great need for additional stem cell lines for which we cannot use NIH funding. If we were going to use non-NIH funding for further research, we would have to be very careful and try to segregate part of the lab as being an entirely separate part from the NIH part. In the long term, no one of knows how the government would interpret the same lab working with so-called approved lines on one side of the lab and non-approved lines on the other side of the lab. Nevertheless, it is our intention to do precisely that."

Kessler is part of a group of researchers, physicians and lawmakers who hope to change not only the national policy on embryonic stem cell research, but also the local one. There is a bill that originated and passed in the Illinois house that would allow embryonic stem cell research to continue in Illinois. In addition, the bill would set guidelines for couples who want to donate unused embryos from in vitro fertilization and calls for an institutional review board that would approve research in the state. The bill hit a roadblock in the state senate with a 28-28 vote. It needs 30 to pass.

"The purpose is to create a new stem cell line that can regenerate tissue or body parts that will not be rejected by the immune system during transplantation."
California and New Jersey legislators passed similar bills regarding stem cell research. In November, California voters will decide whether the state funds should be used to support the research at the tune of $3 billion. And earlier this year, New Jersey became the first state in the nation to allocate state funds to stem cell research by creating the $50 billion New Jersey Stem Cell Research Institute with private partners.

Much of what held the Illinois bill down in the senate was an amendment that would forbid human reproductive cloning. Kessler says concern over human cloning is simply unfounded.

"People confuse therapeutic cloning with reproductive cloning," Kessler explains. "Reproductive cloning is exactly what it sounds like it is, namely cloning a human being. However in somatic cell nuclear transfer [therapeutic cloning], you take an unfertilized egg cell and you take the DNA, or nucleus, out of the egg cell and put the nucleus of the donor cell into the egg cell and use that to generate a new stem cell line. There is no possibility, unless it is implanted into a womb, of this becoming a human being. The purpose is to create a new stem cell line that can regenerate tissue or body parts that will not be rejected by the immune system during transplantation. Besides, no responsible member of the medical or science community would approve of or attempt to clone a human being. It is both technically questionable and unethical."

Rowley uses the example of Dolly the sheep as proof that reproductive cloning is simply not in the forecast.

"We really don't even know enough to create designer babies even if we wanted to," Rowley says. "All of the evidence from experimental animals shows that first, cloned fetuses have a huge mortality rate in utero. Also they tend to be very large. Those oversized fetuses are very difficult for the mother to sustain during birth, creating safety issues for the parent. And then you have Dolly. She had premature aging and died at six years old. So all of experience shows that this may not even be doable for humans, especially since they haven't been able to do it with monkeys. And all of this is beyond the pure ethical issues of human cloning."

The death of President Ronald Reagan has brought the issue of stem cell research back to the forefront of discussion in Washington. Former First Lady Nancy Reagan has become even more vocal about her wish for the federal government to support stem cell research in recent months. In June, 58 senators asked the President to relax his restrictions on embryonic stem cell research, citing President Reagan's death from Alzheimer's as an example of the country's need to participate in the studies. Some of the senators who signed the letter to the president include Democrats Ted Kennedy, Hillary Rodham Clinton and Tom Harkin and Republicans Arlen Specter, Lamar Alexander and Orrin Hatch. In addition, a number of celebrities, among them Dustin Hoffman, Michael J. Fox, Harrison Ford and Warren Beatty, are also challenging the president on his stem cell research policy.

Kessler says this support is crucial to members of the stem cell community.

"It's exceedingly important for the medical community to have that kind of public and political support for stem cell research," he says.

"As a stem cell biologist, it is rather shocking and appalling to find the work we are doing, in which we are trying to help human beings, suddenly being made a political issue where we are potential targets. So having the support of influential people, especially those whose political background would have you think that they would go in the other direction, is great. Seventy percent of the people in this country support broad government support for stem cell research, and it is my hope that in the end the majority of the people will prevail."

"As a stem cell biologist, it is rather shocking and appalling to find the work we are doing, in which we are trying to help human beings, suddenly being made a political issue where we are potential targets."
Some say the lack of support for stem cell research is starting to take a toll on the country's role as a leader in medical and scientific research. This feeling was somewhat solidified in February when a group of scientists in South Korea announced that they not only cloned a human embryo but also extracted stem cells from the blastocyst.

"The NIH, the main source of medical research funding in the country, is prohibited from funding research for embryonic stem cell research," Rowley explains. "So if you ask me to prove that embryonic stem cells are better for regenerating tissue than adult stem cells, I don't have proof that its better because we don't have the research. We don't have answers that we should have had years ago. Some American scientists have gone out of the country to do their research because of this. I think it's shocking that the first cloned embryonic stem cell lines were created in South Korea."

Opponents of embryonic stem cell research say that experimenting on embryonic stem cells is the equivalent of killing babies. But proponents argue that the embryos that would be used for the research are already created and would otherwise be discarded by couples who no longer have a need for them in in vitro fertilization clinics.

Policies on stem cell research could change as early as January 2005, if President Bush loses the November election. Presidential candidate John Kerry supports embryonic stem cell research.

"It is my hope that by the end of November we will have a state bill regarding stem cell research, and we all recognize that the outcome for the federal election will have a direct impact this," says Kessler. "Kerry has already stated that he would overturn President Bush's decision so we should expect almost overnight a more reasonable policy. If Bush is reelected, I will anticipate a long battle."

Published: August 01, 2004
Issue: Fall 2004