Special Article: Stem Cell ResearchAn Overview of Stem Cell Research and Regulatory Issues
Section snippets
EMBRYONIC STEM CELLS
Some stem cells have a greater capacity of self-renewal and multilineage differentiation than others (Table 1). At the time of conception, the fertilized egg (zygote) contains dividing cells (blastomeres) that form an embryo and placenta (Figure 1). These blastomeres are totipotent; they have the potential to form an entire living organism. After about 4 days, these totipotent cells begin to specialize and form into a hollow ball, the blastocyst, containing an outer shell (trophoectoderm) and a
ADULT STEM CELLS
It is generally accepted that each organ of our body is in balance between degradation and repair. The liver that we were born with is not the same liver that we have when we die. Throughout life, toxic insults wound our organs, bringing about the question of what keeps the balance between destruction and construction. In adults, stem cells have been found in many tissues, such as liver, bone marrow, pancreas, and brain, maintaining this homeostasis. Moreover, some of these adult stem cells,
LIVER
One of the first discoveries in end-organ repair and cell plasticity occurred in the liver. When hepatocytes are prevented from proliferating in response to liver damage, hepatic oval cells come to the rescue and produce more hepatocytes and bile duct cells. Interestingly, these oval cells, viewed as resident liver progenitor cells, share similar protein production with the HSC (namely, CD34, c-kit, Thy-1, and flt-3 receptor). This led Petersen et al37 to discover, through transplantation
PANCREAS
The liver and pancreas have close ties, going back to development in which both emerge from the same general area of the ventral foregut endoderm.65 The pancreatic progenitor cell, located within the ductal epithelia of the pancreas, has the capacity to differentiate into endocrine islets of Langerhans, including the glucagon-producing $aL cells, the insulin-producing ß cells, the pancreatic polypeptide-producing $gM cells, and the somatostatin-producing $dL cells.66 Given the close
KIDNEY
Unlike the liver and pancreas, the kidney progenitor cell has yet to be discovered. During development, the human kidney results from collision of the ureteric bud (lower urinary tract) and the metanephric mesenchyme (upper urinary tract). Precursors for the collecting tubules reside within the ureteric bud, whereas precursors for the rest of the kidney come from the metanephric mesenchyme. After development, in situations of injury, the kidney undergoes repair, with myofibroblast cells
HEART
Adult cardiac muscle regeneration is modest and largely restricted to viable myocardium.73 Several investigators have sought to enhance the heart regeneration challenge by injecting different cell sources into damaged myocardium and observing for engraftment. Cell sources such as cell lines, skeletal muscle myoblasts, and bone marrow cells have been used.74, 75 Interestingly, these cellular cardiomyoplasty approaches have identified the bone marrow as one of the richest founts of cardiac
BRAIN
Animal studies of the brain have found that bone marrow can differentiate into neurons and glial cells.84, 85, 86 Whether these transplanted cells are functional and impact cognitive function has yet to be determined; however, environmental influences such as ischemia, seizure, learning, and exercise can substantially stimulate hippocampal neuropoiesis.87, 88, 89, 90 In humans studies, we54 and others53 have found that bone marrow can make brain cells. Female patients undergoing therapeutic
BLOOD VESSELS
The close ties between blood and blood vessels have always been suspected given the recognition of a hemangioblast in the developing embryo. However, whether an adult hemangioblast worked double-duty, replenishing blood and repairing vessels, was debatable until 2002, when Grant et al38 formally proved that the adult HSC can function as a hemangioblast. Furthermore, these investigators were the first to show functional plasticity, with active perfusion of donor-derived vessels. Follow-up
STEM CELLS AND CANCER
In addition to their role in responding to physiologic repair, stem cells are implicated in certain cancers. This conviction is still being deliberated; however, lines of evidence seem compelling. Cancer cells have the ability to selfrenew much like stem cells. In human acute myelogenous leukemia studies, Bonnet and Dick99 have shown that the acute myelogenous leukemia stem cell could be purified from the CD34+CD38– fraction—the same fraction as the HSC. Solid tumors like lung cancer also have
Conventional Indication for HSC Transplantation
Mr S is a 36-year-old accountant who was in otherwise excellent health until increasing fatigue and left upper quadrant abdominal discomfort brought him to his family practitioner. Noting lethargy and splenomegaly, the physician ordered a complete blood cell count, results of which were an elevated white blood cell count of 81,000/$mUL (81.0 × 109/L), no basophilia, a hematocrit of 23%, and a platelet count of 12,000/$mUL (12.0 × 109/L). Bone marrow evaluation showed hypercellularity with
ETHICAL AND REGULATORY ISSUES IN STEM CELL RESEARCH
New discoveries in stem cell biology will soon bring revolutionary changes in the way physicians approach degenerative diseases, wound repair, autoimmune conditions, cancer, and reproductive medicine. Stem cells are self-renewing cells capable of producing many different cell types. Adult stem cells do well in repairing their organ of origin but have limited capabilities in self-renewal and distant organ repair under normal physiologic conditions. The degree of plasticity potential of the adult
CONCERNS REGARDING THE USE OF STEM CELLS
Certainly, stem cells are not the first human discovery to stretch the boundaries of medical knowledge and create waves of ethical debate. Since ancient times, society has admonished man for approaching these boundaries, eg, the Greek myth of Icarus who did not heed his father's command; he reveled in the “unnatural” sensation of flight and then plummeted to his death after the sun melted his wings. This Greek myth embodies our apprehensions about meddling with nature. Galileo Galilei, who
MORAL AND LEGAL STATUS OF THE HUMAN EMBRYO
Many religious perspectives consider the human fetus to constitute an individualized human entity. However, there is substantial debate regarding at which specific stage dignity is conferred in development (conception, primitive streak development, implantation, “quickening,” or birth).106, 107, 108, 109, 110, 111, 112 Recently, a less specific “developmental view” of moral status surfaced, meriting moral rights to the individual as consciousness and relationships develop.113, 114
Taking into
THERAPEUTIC AND REPRODUCTIVE CLONING
The embryonic stem cell also has tremendous potential in producing replicate tissues and genetically identical offspring. Cloning is accomplished by removing the chromosomes of an oocyte, inserting the nucleus of a donor adult (somatic) cell, and then stimulating the hybrid cell to divide as if it were a totipotent zygote. The cell is then prepared to produce any tissue of the body (therapeutic cloning) or if implanted in a female uterus to produce offspring with the same genetic material as
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