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Stem Cells and the Future of Regenerative Medicine
Embryonic stem cells (ESCs) are derived from an early-stage embryo. Fertilization of an ovum by a sperm results in a zygote, the earliest embryonic stage (Figure 1). The zygote begins to divide about 30 hours after fertilization and by the third-to-fourth day, the embryo is a compact ball of 12 or more cells known as the morula. Five-to-six days after fertilization, and after several more cycles of cell division, the morula cells begin to specialize, forming a hollow sphere of cells, called a blastocyst, which is about 150 microns in diameter (one-seventh of a millimeter). The outer layer of the blasotocyst is called the trophoblast, and the cluster of cells inside the sphere is called the inner cell mass. At this stage, there are about 70 trophoblast cells and about 30 cells in the inner cell mass. The cells of the inner cell mass are multipotent stem cells that give rise to all cell types of the major tissue layers (ectoderm, mesoderm, and endoderm) of the embryo. In the past 3 years, it has become possible to remove these stem cells from the blastocyst and maintain them in an undifferentiated state in cell culture lines in the laboratory (NIH, 2001) (Figure 2). To be useful for producing medical therapies, cultured ESCs will need to be differentiated into appropriate tissues for transplantation into patients. Researchers are just beginning to learn how to achieve this differentiation.
Fetal stem cells are primitive cell types in the fetus that eventually develop into the various organs of the body, but research with fetal tissue so far has been limited to only a few cell types: neural stem cells, including neural crest cells; hematopoietic stem cells; and pancreatic islet progenitors. Neural stem cells, which are numerous in the fetal brain, can be isolated and grown in an undifferentiated form in culture, and they have been shown to differentiate into the three main types of brain cells (Brustle et al., 1998; Villa et al., 2000). These cells have been used in rodent models of Parkinson’s disease (Sawamoto et al., 2001; Studer et al., 1998). Neural crest cells arise from the neural tube and migrate from it throughout the developing fetus. They are able to develop into multiple cell types, including the nerves that innervate the heart and the gut, non-neural cells of hormone-secreting glands, pig-