Exciting frontier in medicine

  • Health
  • Sunday, 24 Aug 2003

Stem cell research is an area of medicine that holds much promise for medical breakthroughs. But there are many obstacles, both technical and ethical. The journey to stem cell fulfillment is a long one, but there have been some early successes despite the odds, observes PAUL YEO

HOPE encourages. It gives support to individuals facing prohibitive obstacles and odds. Hope offers a future, albeit an uncertain one. Hope, a good thing to feel when you’re given a scary diagnosis – it tells us that all is not lost, that there might be a way out, a treatment that can overcome the disease.  

Many of us are deeply hopeful that science will one day cure cancer, diabetes, Parkinson’s, Alzheimer’s and so on. And part of the science that offers us such hope involves stem cell research.  

Some of the human body’s most challenging mysteries are being tackled head on in the laboratories of some of the world’s most acclaimed scientists. Ideas abound, and for each success, there are many failures. But the knowledge gained from such work is, hopefully, leading to a solution to many of the secrets of hitherto incurable diseases.  

Diseases and disorders that are incurable, or can only be controlled with therapies, are the lure of the pursuit of stem cell research. Though the basic premise for the research is theoretically sound, there are many technical hurdles between the promise of stem cells and the realisation of its uses. These can only be surmounted by continued intensive research.  

Culture trays containing human embryonic stem cells for research.

There are many areas of medicine where stem cells can be used for therapy. Let’s look at some of the possibilities. 


Organ boost 

Perhaps the most potent application of stem cell research is in replacing cells affected by disease. Some of the diseases that have been identified as possible beneficiaries of such research include Parkinson’s disease, neurological disease, diabetes, chronic heart disease, end-stage kidney disease, liver failure and cancer. And the list may grow, depending on the outcome of further research. 

At present, most of these diseases cannot be cured. So, instead of focusing on treating the pathology, a shift in therapy towards replacing the diseased cells could well be more effective. This shift is seen in replacing damaged tissues or organs through transplants.  

Unfortunately, the numbers do not add up as sufferers far outnumber donors, and the long-term outlook is not an optimistic one. Hence, stem cell research offers hope in this regard. In theory, the cells could regenerate into specialised cells to replace the function of cells already affected by disease. They offer the possibility of a renewable source of replacement cells for damaged cells.  

For example, those suffering from heart failure could hope for stem cell transplants. It may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research into this has been carried out. For example, doctors at the Texas Heart Institute and the Federal University in Rio de Janeiro took stem cells from the bone marrow of patients who had severe heart disease and injected it directly into the heart muscle of patients. The results of the study were published in the American Heart Association journal Circulation

“These patients were desperately ill,” said Dr James Willerson, who led the trial on 21 Brazilian patients. “They had a relatively high risk of dying and had no other forms of therapy available because their heart failure was so severe.”  

Doctors injected 14 of the 21 patients’ hearts with stem cells obtained from their own bone marrow. After two months, patients who underwent treatment had significantly less heart failure and angina. Their hearts were also able to pump more blood around their body. The improvements were still visible four months after treatment.  

Dr Willerson said the trial would have to be replicated in larger clinical trials before doctors elsewhere could carry out the procedure. “This is one of the largest series of stem cell treated patients reported so far. If our findings are confirmed in larger trials, this procedure could lead to an effective treatment for severe heart failure.”  

In another study with positive results, tests in mice showed that a type of stem cells found in blood vessels could help people with a particular form of muscular dystrophy called limb-girdle muscular dystrophy. Muscular dystrophy is a group of progressive, genetic diseases in which the muscles that control movement (called voluntary muscles) degenerate and weaken. 

Dr Giulio Cossu, of the Stem Cell Research Institute in Milan, Italy, who led the research, said: “Although these results are exciting, we have not cured the mice.  

“We believe this is a significant step toward therapy, but the question that keeps me awake at night is whether this will work in larger animals. I’m convinced this is an important result, but this is still not the therapy – for the mice or for patients.”  

Another study, by Dr Walter Low and his colleagues at the University of Minnesota Medical School, involved tests carried out on mice to see if stem cells could indeed turn into other brain cells. In the study, which was published in the journal Cell Transplantation, they injected stem cells, taken from adult mice, into a mouse blastocyst – a mouse in the early embryonic stage. Tests showed these transplanted cells had developed into nerve cells.  

Further analysis showed they had grown in areas of the brain that are generally affected by a range of diseases, including Parkinson’s, multiple sclerosis, Huntington’s and Alzheimer’s.  

This study appears to be an important step forward in the bid to use stem cells to cure serious brain diseases.  

Another example is diabetes. In somebody who suffers from Type I diabetes, the cells of the pancreas that normally produce insulin are destroyed by the person’s own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for diabetics.  

A team from the Howard Hughes Medical Institute in the US is working on stem cells to develop into beta cells when mixed with a hormone found naturally in the human intestine. The same hormone appears to make beta cells secrete insulin.  

Dr Joel Habener, who leads the study, said that if such beta cells can be grown from a patient’s own stem cells and transplanted, the risk of rejection is gone. The study was published in the journal Endocrinology. While such research offers hope, there’s still a lot of work to be carried out. Technical challenges remain, and if these were to be overcome, there’s still the prickly problem of translating these technologies into actual medical practice. Scientists and researchers will have to ensure that stem cells can be made to: 

  • Multiply extensively and generate sufficient quantities of tissue. 

  • Differentiate into the desired cell type. 

  • Survive in the recipient after transplant. 

  • Integrate into the surrounding tissue after transplant. 

  • Function appropriately for the duration of the recipient’s life. 

  • Avoid harming the recipient in any way. 

    There’s also the problem of immune rejection, similar to that in organ transplantation. As human stem cells are derived from embryos or foetal tissue, they would be genetically different from those of the recipient, and such problems will also have to be solved.  


    Genetic research and therapy 

    Gene therapy is a relatively recent and still highly experimental approach to treating human disease. It takes a very different approach to the traditional method of treatment by drugs. Gene therapy directs a patient’s own cells to produce and deliver a therapeutic agent. The instructions for this are contained in the therapeutic transgene (the new genetic material introduced into the patient). Stem cells have been researched as vehicles to deliver therapeutic transgenes into the body.  

    Stem cell research promises the possible development of new therapies for an array of diseases. Hence, research is vital for realising its potential. However, there are still many issues and obstacles to be faced.  

    One thing is clear. Some will be dogged in their effort to tap into this research, as the benefits promise a world where disease will never be the same again, and it could very well revolutionise the practice of medicine and improve quality and length of life. Others are leery of the price – do we compromise morals and ethics for gains that may or may not eventuate? 

    Besides its value for therapy, such research could also bring a better understanding about the processes and controls on the genetic level that lead to conditions such as cancers and birth defects. With a better understanding of such processes, scientists could come up with possible new strategies for tackling such diseases. 


    Drug testing 

    Another area where stem cell research could be of benefit is in the testing of new drugs. At present, drugs that are developed are first tested on animals before undergoing clinical testing in humans. With stem cells, the drugs can be initially tested using human cell lines and observing how they affect those lines. Though this would not replace actual animal or human testing, it could streamline the process, and make it more efficient. Only the drugs that are both safe and appear to have a beneficial effect in cell line testing would graduate to further testing in laboratory animals and human subjects.  


    Where it all begins 

    It is rather appropriate that the potential promise of stem cell research is a direct result of the miracle of life – fertilisation and conception. The transformation of the fertilised egg, from a single cell organism into a complex life form, remains one of nature’s most extraordinary feats. The idea that one single cell can give rise to complex multi-tissue organ systems in the human body such as the brain, spine, heart, kidneys, liver, bones, muscles and so on supports the fact that reality can be more incredible than fiction. 

    But this is real, and the fact that one single cell can turn into so many different cell and tissue types is the premise of stem cell research. Human development begins when a sperm fertilises an egg and creates a single cell that has the potential to form an entire organism. This fertilised egg is said to be totipotent, meaning that its potential is total and that it can eventually evolve into a complex organism that is the human infant.  

    Approximately four days after fertilisation and after several cycles of cell division, these totipotent cells form a hollow sphere of cells, called a blastocyst. The blastocyst consists of an outer layer of cells and an inner cell mass. It is this inner cell mass that will go on to form all the tissues of the human body. The outer layer of cells of the blastocyst goes on to form the placenta and other supporting tissues needed for foetal development in the uterus.  

    The inner cell mass will yield stem cells, a specialised type of cell that gives rise to specific cells such as heart muscle cells, nervous system cells, respiratory cells, renal cells, etc. 

    The stem cell can be described as pluripotent, in that it has the potential to give rise to many other cell types. Alternatively, it can be called a “master” cell, able to become any type of cell that is required in the body.  

    The very fact that a single cell can have such diverse end-points had scientists and medical experts speculating for a long time about the infinite possibilities of the use of such a cell in the treatment of many diseases. After all, if you can grow specialised cells, you can treat diseased organs by implanting the cells into the organ where they will grow brand new cells to replace the diseased ones. 

    It is this cell type that is the focus of stem cell research ever since researchers were able to isolate such cells and grow them in the laboratory for the first time in 1998. Since then, the advances have come fast and furiously, and the possibilities appear limitless. 


    Sources of stem cells 

    Theoretically, there are various sources of stem cells that can be used for research. Stem cells can be directly isolated from the inner cell mass of human embryos at the blastocyst stage. They can also be obtained from foetal tissue harvested from terminated pregnancies. Because of the ethical issues involved in using human embryos for research, much controversy has arisen, with different governments setting in place regulations of differing stringency to control research. 

    The arguments have been such that some proponents of stem cell research have looked at adult stem cells for therapeutic possibilities. Adult stem cells do exist, and are found in bone marrow, cornea, liver, skin, the lining of the gastrointestinal tract and the pancreas. Such cells have been extensively studied, and at this moment, there are many obstacles.  

    First, adult stem cells are rare. They are often difficult to identify, isolate and purify and they do not seem to be able to multiply indefinitely under laboratory conditions, in sharp contrast to those derived from embryos. However, efforts are being undertaken to study adult stem cells and how viable they can be in therapy. 


    Ethics of stem cell research  

    Stem cell research is an ethical time bomb for many. Look at it this way. If the cells are harvested from the tissue of dead foetuses or embryos, the issue of abortion comes up. If they are harvested from cloned embryos, the issue of cloning and “playing god” is sure to surface.  

    Whichever way, it’s a landmine waiting to explode. There is no right or wrong to something as controversial as this. Ethicists can argue until their faces go blue, but at the end of the day, it’s about a balance between benefits and ill effects. It’s hard, especially to the millions who suffer from intractable chronic diseases and who may have real hope of beneficial treatment if research is encouraged.  

    This conundrum has prompted the call for research exclusively focussed on adult stem cells. It has been mentioned earlier that adult stem cells do not appear to be as versatile as stem cells derived from embryos or foetal tissues. However, it has been found in some animal studies that a number of adult stem cells previously thought to only develop into one line of specialised cells are able to develop into other types of specialised cells.  

    For example, recent experiments in mice suggest that when neural stem cells were placed into the bone marrow, they appeared to produce a variety of blood cell types. In addition, studies with rats have indicated that stem cells found in the bone marrow were able to produce liver cells. These findings suggest that adult stem cells could be viable.  

    Furthermore, there are more advantages to using adult stem cells. Adult stem cells mean avoiding the practice of using stem cells that were derived from human embryos or human foetal tissue, sources that trouble many people on ethical grounds. In addition, if the adult stem cell could be isolated from a patient and coaxed to divide and specialise into the required cell type, it is unlikely that such cells would be rejected.  

    There are other issues. Adult stem cells are only present in only minute quantities, and are difficult to isolate and purify. In addition, their numbers may decrease with age. This makes the isolation of such cells even more difficult.  

    Using a person’s own stem cell to treat diseases may sound like an attractive idea, but sometimes, there may not be enough time to grow enough cells to use for treatment. And if a person suffers from a genetic defect, the genetic error would likely be present in his/her own stem cells. Cells from such a patient may not be appropriate for transplantation.  

    The other factor to think about is if adult stem cells were used, who is to say that DNA abnormalities caused by exposure to daily living, including sunlight and toxins, may not have occurred and be present in the adult stem cells?  

    These are all potential problems that make adult stem cell research much less attractive. Only the future will tell whether such research will go ahead.  

    At the end of the day, the promise of stem cell therapies is an exciting one, but significant hurdles remain. Matters can only become clearer as time goes on.  

    In the meantime, we can all only hope, especially for the millions around the globe who suffer from “incurable” diseases. It’s a long road ahead for stem cell research, and results will not be expected to come anytime soon. But what’s left but hope that it comes sooner rather than later? 

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