Chapter 067. Applications of Stem Cell Biology in Clinical Medicine (Part 4)

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Other Organ Systems and the Future The use of stem cells in regenerative medicine has been studied for many other organ systems and cell types, including skin, eye, cartilage, bone, kidney, lung, endometrium, vascular endothelium, smooth muscle, striated muscle, and others. In fact, the potential for stem cell regeneration of damaged organs and tissues is virtually limitless. However, numerous obstacles must be overcome before stem cell therapies can become a widespread clinical reality. Only HSCs have been adequately characterized by surface markers to allow unambiguous identification, a prerequisite for reliable clinical applications. The pathways for differentiating stem cells into...

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Chapter 067. Applications of Stem Cell Biology in Clinical Medicine (Part 4) Other Organ Systems and the Future The use of stem cells in regenerative medicine has been studied for many other organ systems and cell types, including skin, eye, cartilage, bone, kidney, lung, endometrium, vascular endothelium, smooth muscle, striated muscle, and others. In fact, the potential for stem cell regeneration of damaged organs and tissues is virtually limitless. However, numerous obstacles must be overcome before stem cell therapies can become a widespread clinical reality. Only HSCs have been adequately characterized by surface markers to allow unambiguous identification, a prerequisite for reliable clinical applications. The pathways for differentiating stem cells into specific cellular phenotypes are still unknown, the migration of transplanted cells is uncontrolled, and the response of the cells to the environment of diseased organs is unpredictable. Future strategies may employ the
coadministration of scaffolding, artificial extracellular matrix, and/or growth factors to orchestrate differentiation of stem cells and their organization into appropriate constituents of the organ. Imaging techniques are needed to visualize stem cells in vivo after transplantation into humans. Fortunately, stem cells can be engineered before transplantation to contain contrast agents that may make this feasible. The potential for tumor formation and the problems associated with immune rejection are significant impediments. Many strategies for cell replacement already include vasoactive endothelial growth factor (VEGF) coadministration to foster vascularization, which is required for survival and function of the transplant. Some stem cells have been engineered to have an inducible suicide gene so that the cells can be eradicated in the event of tumor formation or some other complication. The potential for stem cell therapies to revolutionize medical care is extraordinary, and disorders such as myocardial infarction, diabetes, Parkinson's disease and many others are attractive targets. However, such stem cell–based therapies are at a very early stage of development, and perfection of techniques for clinical transplantation of predictable, well- characterized cells will be a difficult and lengthy undertaking. Ethical Issues Stem cell therapies raise contentious ethical issues that must be addressed in parallel with the scientific and medical opportunities. Our society has great diversity in religious beliefs, concepts of individual rights, tolerance for
uncertainty and risk, and boundaries for how scientific interventions should be used to alter the outcome of disease. In the United States, the federal government has authorized research using human ES lines in existence before August 2001 but has restricted the use of federal funds for developing new human ES lines. However, these existing lines develop abnormalities with time in culture and are contaminated with mouse proteins. These findings have sparked renewed debate about the need to develop new human ES cell lines. In considering ethical issues associated with the use of stem cells, it is helpful to draw from experience with other scientific advances, such as organ transplantation, recombinant DNA technology, implantation of mechanical devices, neuroscience and cognitive research, in vitro fertilization, and prenatal genetic testing. From these and other precedents, we learn the importance of understanding and testing fundamental biology in the laboratory setting and in animal models before applying new techniques in carefully controlled clinical trials. When these trials occur, they must include full informed consent and have careful oversight by external review groups. Ultimately, medical interventions will be scientifically feasible but ethically or socially unacceptable to some members of a society. Stem cell research raises questions about the definition of human life, and it has raised deep fears about our ability to balance issues of justice and safety with the needs of critically ill patients. Health care providers and experts with backgrounds in ethics, law, and
sociology must help guard against the premature or inappropriate application stem cell therapies, and the inappropriate use of vulnerable population groups. On the other hand, these therapies offer important new strategies for the treatment of otherwise irreversible disorders. An open dialogue between the scientific community, physicians, patients, and their advocates, lawmakers, and the lay population is important to raise and address ethical issues and to balance the benefits and risks associated with stem cell transfer. Acknowledgments The author acknowledges the contributions of David Bodine, J. Larry Jameson, and Ron McKay to this chapter in the 16th edition Further Readings Committee on the Biological and Biomedical Applications of Stem Cell Research et al: Stem Cells and the Future of Regenerative Medicine. Washington, D.C., National Academies Press, 2002 Holland S et al: The Human Embryonic Stem Cell Debate: Science, Ethics and Public Policy. Cambridge, MA, MIT Press, 2001 Lanza R et al (eds): Essentials of Stem Cell Biology. San Diego, Elsevier
Academic Press, 2006 Mimeault M et al: Stem cells: A revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther 82(3):252, 2007 [PMID: 17671448] National Institutes of Health: Stem cell information page. URL: http://stemcells.nih.gov/index.asp. Puceat M, Ballis A: Embryonic stem cells: From bench to bedside. Clin Pharmacol Ther 82(3):337, 2007 [PMID: 17637781] Sugarman J: Ethics and stem cell therapeutics for cardiovascular disease. Prog Cardiovasc Dis 50(1):1, 2007 [PMID: 17631433] Vats A et al: Stem cells. Lancet 366:592, 2005 [PMID: 16099296]