Have you heard about the new revolution in biotech? I’m not talking about the unraveling of the human genome. I’m talking about the recent discovery and isolation of human Stem Cells. Stem cells are the previously hypothesized, elusive cells in everyone’s body capable of transforming into any tissue or organ . Never heard about them? You will. Their potential as a therapeutic agent is unlimited. At the same time, ethical concerns over harvesting these cells from human embryos have brought stem cell science to the forefront of an international controversy. Researchers in many instances need to use human fetal tissue to study human stem cells. Initially it was believed stem cells could only derive the same tissue from which they were harvested; bone stem cells could only transform into bone, skin stem cells into skin and so on. Recent research has determined that any stem cell (blood, skin, liver, etc.) may be able to be transformed into any tissue or organ in the human body, including retina, lens and cornea. It might be possible to use the cells to genetically “remodel” heart, liver, pancreas or brain tissue, theorize scientists.
Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Human development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. This fertilized egg is totipotent, meaning that it’s potential is total. In the first hours after fertilization, this cell divides into identical totipotent cells. This means that either one of these cells, if placed into a woman’s uterus, has the potential to develop into a fetus. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize, forming a hollow sphere of cells called a blastocyst. The blastocyst has an outer layer of cells and inside the hollow sphere, there is a cluster of cells called the inner cell mass. The outer layer of cells will go on to form the placenta and other supporting tissues needed for fetal development in the uterus. The inner cell mass cells will go on to form virtually all of the tissues of the human body. Although the inner cell mass cells can form virtually every type of cell found in the human body, they cannot form an organism because they are unable to give rise to the placenta and supporting tissues necessary for development in the human uterus. These inner cell mass cells are pluripotent – they can give rise to many types of cells but not all types of cells necessary for fetal development. Because their potential is not total, they are not totipotent and they are not embryos. In fact, if an inner cell mass cell were placed into a woman’s uterus, it would not develop into a fetus. The pluripotent stem cells undergo further specialization into stem cells that are committed to give rise to cells that have a particular function. Examples of this include blood stem cells which give rise to red blood cells, white blood cells and platelets; and skin stem cells that give rise to the various types of skin cells Multicellular organisms are formed from a single totipotent stem cell. As this cell and it’s progeny undergo cell divisions, the potential of the cells becomes restricted, and they specialize to generate cells of a certain lineage. In several tissues a stem cell population is maintained in the adult organ, and it may generate new cells continuously or in response to injury Neural stem cells isolated from the adult forebrain were recently shown to be capable of repopulating the hematopoeitic system and produce blood cells in irradiated adult mice.
There are several important reasons why the isolation of human pluripotent stem cells is important to science and to advances in health care. At the most fundamental level, pluripotent stem cells could help us to understand the complex events that occur during human development. A primary goal of this work would be the identification of the factors involved in the cellular decision-making process that results in cell specialization. We know turning genes on and off is central to this process, but we do not know much about these “decision-making” genes or what turns them on or off. Some of our most serious medical conditions, such as cancer and birth defects, are due to abnormal cell specialization and cell division. A better understanding of normal cell processes will allow us to further delineate the fundamental errors that cause these often deadly illnesses. New drugs could be tested using human cell lines, streamlining the process of drug development. Perhaps the most far-reaching potential application of human pluripotent stem cells is the generation of cells and tissue that could be used for so-called “cell-therapies” Many diseases and disorders result from disruption of cellular function or destruction of tissues of the body. Today, donated organs and tissues are often used to replace ailing or destroyed tissue. Unfortunately, the number of people suffering from these disorders far outstrips the number of organs available for transplantation. Pluripotent stem cells, stimulated to develop into specialized cells, offer the possibility of a renewable source of replacement cells and tissue to treat a myriad of diseases, conditions, and disabilities including Parkinson’s and Alzheimer’s diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis. There is almost no realm of medicine that might not be touched by this innovation.
Manipulation of Stem Cells makes it possible to envision a time in the not-to-distant future when, for example, a hair follicle or finger nail of a patient with wet AMD is cultured and stem cells are altered to grow macula and choroid in a petri dish. With the patient’s diseased macular region excised including the choroid, microsurgeons would then reestablish choroidal circulation beneath the macula with healthy, newly grown vessels and implant the new macular region, restoring sight. Physiological lenses could be grown and implanted in the lens capsule in cataract operations, not only restoring sight, but focusing ability, and corneas could be regenerated, reducing or eliminating chances of rejection in PK operations. Myopia could potentially be wiped out with fetal stem cell therapy, but don’t put your Excimer’s in the garbage heap yet. Therapies using stem cell popu
Clarke, D., Johansson, C, Wilbertz, J et al., Generalized Potential of Adult Neural Stem Cells, Nature, 2 June 2000, 288 1660-1663
Howard Hughes Medical Institute, HTML document, http://www.hhmi.org/news/stemcell.html, p. 2
Stem Cells: A primer, National Institutes of health, May 2000, http://www.nih.gov/news/stemcell/primer.htm
ibid, pg. 1660
C.R. Bjornson, R.L. Rietze, B.A. Reynolds, M.C. Magli, A.L. Vescovi, Science 283, 534 (1999)
Stem Cells, A Primer, National Institutes of Health, May, 2000, http://www.nih.gov/news/stemcell/primer.htm, p 3