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STEM CELLS 101 11 markers. In humans, implantation occurs when the trophoblast cells invade the uterine tissue, forming a syncytiotrophoblast·something like a mega-cell. The fetus secretes proteolytic enzymes that dissolve the uterine epithelial cells and degrade the extracellular matrix. Im- plantation protects the embryo and provides its metabolic needs. EMBRYONIC STEM CELLS The ESC is defined by its origin in the embryo. The fertilized egg has unbounded stemness. At this stage it is totipotent and can create all kinds of cells. Totipotency is limited to only one or two divisions. As the egg becomes a blastocyst and before it implants in the uterus, the hollow round ball develops a clump of cells·the ICM·and becomes pluripotent. ESCs are harvested exclusively from this ICM in the blastocyst. When placed in a cell culture in vitro, ESCs differentiate into many kinds of cells, which are shown in all three germ layers. But because the induc- tion or communication process is disrupted between the ICM and the tro- phoblast, the cells can generate only embryonic germ cells that will not become a human embryo. This remarkable feat of the ESC was first shown in the 1980s, using the ICM of a mouse blastocyst. In the culture dish, cell-to-cell commu- nication led to the formation of nerve, skin, and other cells. But without the surrounding layers of the trophoblast, they received no signals from the motherÊs uterus. The cells became like wandering boys, able to make all the necessary differentiated cells but unable to put them together to become living beings. ADULT STEM CELLS The embryo usually becomes a fetus about eight weeks after fertiliza- tion. At this time another type of cell·the adult stem cell·emerges. The discovery that these cells were present in many formed adult tissues and organs changed the paradigm of past assumptions of how the body repairs itself. In the past, it was assumed that skin cells near the area of a cut or scraped knee would rush to repair the offended area. Brain cells, muscles, and some other cells were thought to never repair themselves. But recent research on adult stem cells has changed the picture. The adult stem cell is undifferentiated and unspecialized. However, Table 1.l shows that these adult cells do exist in specialized and differen- tiated tissues and organs. They can renew themselves and differentiate to yield all the specialized cell types of the tissue from which they originate.