STEM CELL RESEARCH AND THERAPY: HOW CLOSE ARE WE, REALLY?
“Stem cells isolated from adult breast tissue” – CTV.ca, Jan 5 2006
“California ‘backs’ stem cell move” – BBC, Nov 3 2005
“Two Studies Bolster Stem Cells’ Use in Fighting Disease” – Washington Post, Sept 27 2005
“Discredited Stem Cell Scientist Apologizes in South Korea” – New York Times, Jan 12 2006
Almost every other day we hear or read something related to stem cell research, may it be scientific, political, or economical, from news reports or newspapers. It seems that stem cell research has become an extremely popular field of study – and not without good cause. First of all, stem cells might serve as a potential therapy for diseases that result from the inability of our body’s cells to replenish themselves after injury or cell death (i.e. diabetes, Alzheimer’s, Parkinson’s, Muscular Dystrophy, spinal injury, heart diseases, etc). Secondly, it appears that some cancers are a result of aberrant stem cell behavior, making further understanding of basic stem cell biology essential to finding more effective treatments for cancer. Understandably, stem cell research has evolved dramatically over the past 10 years. It seems necessary, therefore, to talk about what a stem cell is, what obstacles stem cell research faces, and what attempts have been made to address these obstacles.
So, what exactly is a stem cell? Generally speaking, a stem cell is an unspecialized cell without a defined function that has the ability to: 1. Self-renew, meaning the cells can continuously replicate in its unspecialized form without dying, and 2. Give rise to multiple specialized cell types of the entire organism or a given tissue type. This means, for example, that the same stem cell can possibly transform into blood cells, neural cells, muscle cells, and many more. Usually stem cells are separated into two types: embryonic and adult. Embryonic stem cells are derived from early embryos before they implant and develop into a fetus, while adult stem cells are derived from a mature adult being. The best example of an adult stem cell is the hematopoietic stem cell, which can generate all the different types of blood cells, including red blood cells that carries oxygen, platelets that promotes blood clotting, and various kinds of white blood cells associated with disease fighting. To demonstrate the ability of a stem cell to generate different cell types, words like “pluripotent” and “multipotent” are used. Embryonic stem cells are pluripotent, as they can generate any cell type in an individual except the placenta. Adult stem cells are multipotent, meaning they can generate a large range of cells, mostly in the same organ system, but not every single cell type in an individual. Hence adult stem cells don’t have the same plasticity (a term adopted by stem cell biologists to represent the range of tissue types a cell can produce) as embryonic stem cells. The ability of stem cells to generate a virtually limitless number of cells with many different characteristics make them great candidates when it comes to replacing the cells in medical conditions mentioned previously such as diabetes or spinal injury.
So far it sounds like stem cells could be a miracle treatment for many costly, (with respect to both human lives as well as medical expenses), medical conditions. So why haven’t we seen a wide spread use of stem cell therapies in clinical treatments? The reason has both social and scientific roots. The major ethical issue with stem cell research originates from embryonic stem cell research. This is because of the fact that majority of the embryonic stem cells are taken from embryos that still have the ability to develop into a fetus, and the procedure used to generate embryonic stem cells will essentially kill the embryo in the process. Hence many groups, especially religious communities, object to the use of embryonic stem cells for research. Should these embryos be considered as individuals? Does the destruction of very early embryos equate to destroying life? Can we generate embryos for the purpose of research but not creating life? Essentially the argument ends with the big question, “when does life begin?” – and that is one that I don’t have the chance to further discuss in this short piece. Until there is universal agreement with this issue, it is less likely that embryonic stem cell research, especially in humans, will be accepted by all groups. Interestingly, scientists have recently begun to address this issues not from the ethical/social/religious aspects, but through the development of new techniques to generate stem cells.
Recently two articles published in the Jan 12th, 2006 issue of Nature demonstrated the possibly to generate less ethically refutable embryonic stem cell lines. Before a fertilized egg develops into an embryo, it goes through several stages of cell divisions and form a cell cluster called morula; each cell inside the morula is called a blastomere and the morula continues to form a “blastocyst.” A blastocyst, which is where embryonic stem cells are usually derived from, is capable of implanting in the uterus. Lanza and colleagues from Advanced Cell Technology developed a technique to remove one blastomere from the 8-cell stage mouse morula, and use that blastomere to generate several embryonic stem cell lines. This technique is already being used as a way to detect genetic defects of in vitro fertilized embryos. They also found that the rest of the blastomeres could continue to develop into an implantable blastocyst with a normal rate, showing that the embryo was not destroyed or damaged and could continue to develop unharmed. Another group led by Meissner and Jaenisch from MIT used genetic manipulation technique to generate a blastocyst that in essence could not implant in the uterus and hence is NOT an embryo. Nevertheless, one could still derive embryonic stem cells from the blastocyst by reversing previous genetic manipulation. Although it is uncertain whether the same scenarios can apply to human embryonic stem cell research, this is an important step in solving ethical issues with advance scientific techniques. It certainly won’t be anytime soon since research in human embryonic stem cells will have to be available first.
Other than the ethical issues surrounding the use of embryonic stem cells for research, there are still many scientific difficulties in actually using embryonic stem cells for clinical therapy. First of all, because a stem cell is an unspecialized cell, there are many stages before it can differentiate on command into a final stage cell such as a neuron, a skin cell, or a muscle cell. And there are also many factors involved in keeping the cell in its final stage. Hence, the correct ”stop” and “go” signals need to be worked out first. Otherwise we risk using cells that are unstable – and, let your imagination go wild here, – we certainly do not want to find skin cells inside our brain after stem cell therapy! Right now, the majority of research with embryoinic stem cells is focused on using them as cell replacement therapy in medical conditions such as diabetes, spinal injury, Alzheimer’s, etc. A strong caveat of this approach, though, is that the ES cells used are from another donor. The recipient of such embryonic therapy will very likely have to receive immunosuppressive. Immunosuppressive therapies compromises the recipient’s immune system, and therefore prevent the recipient’s body from rejecting cells and tissue from the donor. However, immunosuppressive therapy causes an increased chance of infection, not to mention the accumulative long-term cost of this lifelong therapy. Therefore it is necessary to establish techniques to generate recipient-tailored embryonic stem cells before ES cell therapy can be widely applied. Theoretically speaking, such embryonic stem cells can be generated by a technique called nuclear-transfer: the patient’s genetic material inside the nucleus of his or her cells is transferred into a donor oocyte (egg) to generate an embryo with the patient’s own genetic profile. Cells generated from this stem cell will have the same characteristic as recipient cells and therefore can fool the recipient’s immune system and prevent immune rejection. And that is why the paper published by the Korean group led by Dr. Hwang Woo-Suk from Seoul National University in the June 17th, 2005 issue of Science attracted so much attention. If successful, it would be the first time that nuclear-transferred, patient-specific human embryos were generated. Although this article was eventually found to be a fraud that disturbed the whole scientific community, it clearly demonstrated how desperate we are to seek progress in this area – a whole other article can be written on this topic, I am sure. Another option is to use adult stem cells derived directly from the patient. Even here, there are certainly limits to the plasticity and self-renewal ability of adult stem cells. If this limitation can be removed, then adult stem cells might serve as an alternative to embryonic stem cells.
It is without question that stem cells hold tremendous therapeutic potential, yet additional research is essential to move us closer to clinical benefits. At the same time, we should keep in mind that ethical issues will need to be addressed before we will see routine use of stem cells as treatments. It is inspiring to see many efforts being made to resolve these pertinent ethical issues. It is my hope that one day I will live to see a comprehensive and equitable agreement that could allow us to translate science into life-saving treatment.