ABSTRACT
Stem cells are capable of both self-renewal and differentiation into more specialized cells and tissue, and are broadly categorized as either embryonic stem cells (ESCs) or adult stem cells (Figure 33.1abc). Fertilization results in the generation of totipotent cells that can form both the placenta and all tissues within the developing fetus. The initial differentiation of post-fertilized totipotent cells leads to the delineation of an outer layer of trophoblast that develops into the placenta, and an inner cell mass (ICM) of multipotent ESCs that can differentiate into all three germ layers: mesoderm, endoderm and ectoderm. An ESC line may be obtained by culturing the ICM over a feeder layer of embryonic fibroblasts1-3. One disadvantage of ESCs is a tendency to form teratomas when injected in vivo4,5. This complication may be overcome by ex vivo-directed differentiation of ESCs into adult stem cells prior to in vivo application5. Another disadvantage of using ESCs in clinical studies is that current culture requirements for a feeder layer and/or feeder-layer supernatant extract must be overcome to meet Food and Drug Administration (FDA) requirements for human application. While ESCs may be differentiated into neuronal stem cells, neurons or oligodendrocyte progenitor cells6-8, clinical trials in
America will depend on developing ex vivo culture and expansion techniques that will satisfy FDA requirements for human trials. Therefore, for the rest of this chapter, we focus on adult hematopoietic stem cell sources in current clinical transplant trials.
