Stem Cell Search Offers Hope

According to a ScienCentralNews article by Karen Lurie, “Nancy Reagan says she plans to devote herself to pushing for federal support of stem cell research which scientists believe could lead to a cure for Alzheimer’s disease. With Ronald Reagan’s death she’s expected to be more aggressive in asking the Bush administration to reverse its ban on funding stem cell research involving human embryos – a policy that led one leading American scientist to move his lab overseas.”

Stem cell research offers hope for people with many diseases and disabilities. According to the National Institutes of Health (NIH), “Stem cells offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.”

What is a stem cell? Dr. Ted Eastlund, Co-Director of the Division of Transfusion Medicine at the U of M Medical School puts it this way: “Stem cells can grow into almost any other cell depending on what you ‘feed’ them. Stem cells could become nerve cells, for grafting to the site of a spinal cord injury, or brain cells, for treating Parkinson’s disease.” However, research is needed to realize this potential, as there is currently only one non-experimental use for stem cells.

Dr. Eastlund explains: “The only real successful stem cell transplants are those used for marrow transplant (e.g., for treating leukemia etc). These hematopoietic (growing into blood cells) stem cells can be obtained by getting a piece of marrow, grinding it up, and infusing it into the patient like a blood transfusion. The stem cells know enough to go to the patient’s marrow, settle in and grow, and give the person an entire new blood system and immune system.”

Dr. Eastlund describes one area of current research with blood stem cells: “Injecting stem cells around an area of myocardial infarction in the damaged heart muscle is strictly experimental, but they want to try it at Abbott Northwestern. It is hoped that the injected stem cells will help new heart muscle grow.” Dr. Eastlund referred me a May 2004 article from the Annals of Internal Medicine, which reads in part:

“Stem cell transplantation in acute myocardial infarction is still in its infancy. The potential for stem cells to acutely regenerate contracting myocardium and improve immediate and long-term prognosis after acute myocardial infarction faces some formidable challenges. Whether stem cell transplantation offers a sustained clinical benefit by reversing ventricular remodeling is unknown, given that too few patients have undergone stem-cell transplantation to derive any meaningful efficacy and safety data.”

The source of the stem cells gives rise to the controversy. Fully developed donors are one source; Dr. Eastlund describes another: “Blood stem cells can also be obtained from [umbilical] cord blood. After a baby is delivered, the placenta is taken and blood removed via the attached cord. It is rich in stem cells.”

With the availability of stem cells from other sources, why conduct research with fetal or embryonic stem cells at all? There would be little reason if all stem cells were created equal, but they are not. Cord cells and cells from fully formed donors are adult stem cells, and according to NIH, there are significant differences between adult and embryonic stem cells.:

“Embryonic stem cells can become all cell types of the body . . . Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin.” NIH cites another difference: “Large numbers of embryonic stem cells can be relatively easily grown in culture, while adult stem cells are rare in mature tissues and methods for expanding their numbers in cell culture have not been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.”

Currently, there are fewer than 20 ” lines” of embryonic stem cells approved for federally funded research. Each line of cells originated from a different embryo. NIH explains: ” When cells replicate themselves many times over it is called proliferation. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells.”

Researchers are concerned not only with the lack of genetic diversity of these few lines of embryonic stem cells, but about their safety for therapeutic use.

According to a Dec. 2003 article by Merrill Goozner, the biggest fear among researchers is that mouse-fed cell lines, which include all the lines approved by President Bush’s 2001 edict, may contain unidentified retroviruses that can cause havoc if they cross species. ‘Probably none of those cell lines should go into clinical studies,’ said Eugene Redmond, Yale University. ‘Why spend money and waste time with a cell line that you’re not going to be able to use for therapy?”

AIDs is one example of a retrovirus that is thought to have crossed species to humans from other primates. As for what is meant by a mouse-fed cell line, NIH explains: “The inner surface of the culture dish is typically coated with mouse embryonic skin cells that have been treated so they will not divide. This coating layer of cells is called a feeder layer. The reason for having the mouse cells in the bottom of the culture dish is to give the inner cell mass cells a sticky surface to which they can attach. Also, the feeder layer cells release nutrients into the culture medium.”

NIH notes: “Recently scientists have begun to devise ways of growing embryonic stem cells without the mouse feeder cells. This is a significant scientific advancement because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.”

But in a May, 2004 letter, NIH director Elias Zerhouni seemingly contradicts the information on his organization’s website. According to the May 20, edition of The Scientist online: “In the letter, Zerhouni argues that there’s no proof stem cells grown on human feeder layers would be safer than mouse-fed cells.”

No proof perhaps, but using human feeder layers would clearly eliminate the possibility of transmitting a mouse virus to humans. If the director of the Neural Transplantation and Repair Program at Yale thinks mouse-fed stem cells are potentially unsafe – readers may draw their own conclusions.

On expanding the number of available cell lines, The Scientist quotes Zerhouni, “From a purely scientific perspective, more cell lines may well speed some areas of HESC [human embryonic stem cell] research.’ But he restated the administration’s position that ‘taxpayer funds should not sanction or encourage further destruction of human embryos that have at least the potential for life.”

Where do embryonic stem cells come from, and how much potential for life do they have? According to the NIH: “The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor.” A press release from the University of California, reads in part: “At this stage, the embryo, known as a blastocyte, contains no distinctive body tissues, and would never be transplanted into a woman’s womb. The stem cells would be obtained from this mass.”

Past research involved fetal stem cells, but since embryonic cells where first isolated in 1998, they have been the focus of non-adult stem cell research. By the fetal stage of development, cells have differentiated, becoming skin, bone, internal organs, etc. Embryonic stem cells are harvested at a much earlier stage, according to NIH:”The embryos from which human embryonic stem cells are derived are typically four or five days old and are a hollow microscopic ball of cells called the blastocyte.”

Besides the limited number of stem cell lines, lack of funding hampers research. The Scientist quotes NIH director Zerhouni’s letter: “He also writes that the NIH spent $24.8 million on human embryonic stem cell research in fiscal year 2003, a 132% increase over the previous year. AIra Black, director of the Stem Cell Research Center at Robert Wood Johnson Medical School in Camden, NJ, said that figure was >modest in the extreme,” according to The Scientist.

“Britain’s investment in stem cell research took a major step forward this week with the news that a further 16.5 million (pounds sterling) is being issued in grants,” according to the May 28 edition of The Scientist. With an economy a fraction the size of ours, Britain has just increased it’s stem cell research funding by more than the total amount of US funding for fiscal 2003.

The Scientist reported that Britain’s Medical Research Council (MRC) will receive some of these funds and quoted chief executive Colin Blakemore as saying: “Compared to some other areas of science, this is one where the UK has an edge because of our relatively compliant legislative framework.”

Amidst the controversy surrounding embryonic stem cells, exciting work is also progressing with adult cells. “Researchers are developing a method of transplanting nose cells into the spinal cord of paralyzed patients to help them walk again,” according to Liam McDougall, health correspondent for the Sunday Herald online. Adult nasal stem cells generate new nerve cells, maintaining our sense of smell as we age. These cells are taken from the patient and grafted to the site of the spinal injury in the hope of rebuilding the severed cord.

One advantage of using the patient’s cells is that, unlike transplants from other donors, they are not rejected by the immune system, so immunosuppressive drugs are not needed. These drugs must be taken for the rest of the patient’s life to avoid transplant rejection, and their suppression of the immune system can increase susceptibility to other infections and diseases.

McDougall reports this research is underway at Scotland’s Glasgow University, suggesting our limited federal funding may be causing the US to fall behind Britain in realizing the potential of adult stem cells as well as those obtained from embryos. Arguments against destroying anything with the potential for human life don’t apply to adult cells. Who would deny a patient’s right to use their own cells to heal a damaged heart or spinal cord?

The facts surrounding harvest of embryonic stem cells from donated blastocysts may ease ethical opposition. The blastocysts in question were fertilized in petri dishes with the intent of creating, not destroying life. Several blastocysts are grown in the hope of achieving one pregnancy. Whether due to the birth of a child, or to several unsuccessful attempts, the donor decided that the remaining blastocysts would never be implanted into her womb. She then chose to donate the remaining blastocytes to science, potentially benefiting humanity, rather than waste them.

The US doesn’t actually ban research using stem cell lines other than those few the government has approved; it does however, ban federal funding for such research. The Scientist reports that “(Ira) Black is the director for Stem Cell Research in New Jersey, which would be funded by the state,” and notes that, “California is considering a bond issue for a similar effort.’ The Scientist quotes Black: “This may be a wave of the future, in which individual states jump in to fill the void.’

This November, Californians will vote on $3 billion in state funding for stem cell research, according to The Scientist online. If passed, California would become the world’s leading financier. California Senator Deborah Oritz: said “Although there may be a debate on whether this initiative is a fiscally sound decision for the state, the potential cuts in healthcare costs would more than pay for the investment over time.”

“More people are impacted by [degenerative] diseases than by any war or terrorist attack, therefore we should be spending more money trying to cure and prevent them,” The Scientist quotes Larry Goldstein, professor University of California, It should be a national priority.”

Black and others said that larger efforts are needed. “This research needs federal funding,’ said Bernard Siegel, of the Genetics Policy Institute.”

An aging population including more people with disabilities fuels skyrocketing medical costs, threatening Medicare’s future solvency, and raising the question: Can we afford not to fund stem cell research.