Are Stem Cells and Genetic Therapies Ready for “Prime Time”?
Article Outline
Please make no mistake about it: I am not a molecular biologist. When I went through medical school and subsequent training in internal medicine and cardiology, molecular biology had not been invented. Moreover, computed tomography, magnetic resonance imaging scanners, and echocardiography were in early development. Nevertheless, it is important for me and for other clinicians to understand the rudiments of molecular biology as it relates to promising future therapies. Examples are stem cell therapies and genetic interventions.
Recently, I was feeling guilty about my ignorance of these fields and tried to rectify my intellectual deficit by attending professional society sessions and by reading a number of books and articles aimed at updating physicians on the remarkable scientific advances of the last 25 years.1, 2, 3, 4, 5 The future possibilities for therapies based on stem cells or the modification of abnormal genes include correction of diseases such as sickle cell anemia, diabetes mellitus, and the various forms of muscular dystrophy. Also under investigation are treatments that might allow regeneration of nerve, muscle, and myocardial tissues in patients who have suffered injury or other destructive processes.
Stem cells are pluripotential entities; that is, they are capable of developing into a variety of different cell types, thereby creating new banks of tissue for transfer into a damaged organ. For example, recent clinical experiments have involved attempts to grow new myocardial cells in injured myocardium. In addition, exciting work has been done on creating zones of normal hematopoietic cells in the bone marrow of children afflicted with sickle cell anemia.
We all had pluripotential stem cells in abundance during early embryonic life. Today, molecular scientists can harvest embryonic stem cells from an early stage of human fetal development without hurting the developing fetus. These harvested cells can than be induced to grow on an artificial medium in the laboratory. Moreover, the blood contained in the umbilical cord of a newborn contains stem cells, which can easily be collected from the cord and placenta after birth. Finally, even adult humans have some stem cells located in various tissues, especially in the bone marrow. However, adult stem cells are less plastic than those derived from an early stage of human fetal development or cord blood, and therefore, their therapeutic potential is more limited.
Of course, the use of fetal cells raises many ethical questions that have received a great deal of attention in both the scientific and the lay press in recent years. Discussion of these issues requires considerably more space than is available here. In the meantime, let us assume that some socially acceptable method of stem cell harvest will ultimately be available for clinical therapeutics.
To date, a number of groups have attempted to infuse or inject stem cells derived from bone marrow or skeletal muscle into necrotic and ischemic myocardium in patients who have suffered a recent myocardial infarction.4, 5 The results have been positive in certain trials and without effect in others. In some patients, newly developed zones of myocardium have developed intrinsic electrical activity that spurred malignant ventricular arrhythmias, requiring placement of an implantable cardioverter defibrillator. Bone marrow transplantation for patients with sickle cell anemia has had some limited success but is far from becoming a routine therapy.
Clinical attempts to alter defective genes by injecting virus particles that transport corrective DNA have also been fraught with problems, including fatal reactions to the viral carrier. Despite morbidity and mortality in early trials, investigators are convinced that such interventions will eventually offer tremendous benefit for many thousands of patients, including those afflicted with cystic fibrosis or any of a variety of congenital, inherited, pathological entities.
Another unfortunate outcome of early research into stem cells and gene therapy is scandal—most recently, the disclosure that provocative stem-cell data from a South Korean team had been manufactured. The news media have feasted on these incidents, although dishonest individuals represent a tiny fraction of the dedicated and thoroughly reliable scientists working toward breakthroughs.
I believe these research areas do hold great potential. However, we have a long way to go before such therapies will be ready for prime time. The situation is not unlike early attempts to put an American astronaut into orbit. Many early rockets exploded on the launching pad, and recent events have shown that there remains a substantial risk of death even for current space explorers. Still, we expect the National Aeronautics and Space Administration to continue pushing further into the universe.
Similarly, today’s research into stem cells and gene replacement will eventually provide many valuable therapeutic interventions. While it may be decades before such therapies can be safely and efficaciously employed in everyday clinical care, I am convinced that such therapy will one day be standard enough to be taken for granted—just like our ability to travel to the moon.
References
- . The Stem Cell Divide. New York, NY: AMACOM; 2006;
- . Stem cells. Lancet. 2005;366:592–602
- . Adult stem cells for tissue repair—a new therapeutic concept?. N Engl J Med. 2003;349:570–582
- . Stem cell repair of infarcted myocardium (An overview for clinicians). Circulation. 2003;108:1139–1145
- . Progenitor and embryonic stem cell transplantation for myocardial angiogenesis and functional restoration. Eur Heart J. 2003;24:404–411
PII: S0002-9343(06)01399-4
doi:10.1016/j.amjmed.2006.12.001
© 2007 Elsevier Inc. All rights reserved.
