Types of stem cells 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 (Fig. 44.1). Fertilization of the oocyte 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 pluripotent 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 fibroblasts.– A major disadvantage of ESCs is a tendency to form teratomas when injected in vivo., This complication may be overcome by ex vivo-directed differentiation of ESCs into adult stem cells prior to in vivo application. Another disadvantage of using ESCs in clinical studies is that current culture requirements for a feeder layer and/or xenogenic-derived products for maintenance culture must meet Food and Drug Administration (FDA) requirements for human application. While ESCs may be differentiated into neuronal stem cells, neurons, or oligodendrocyte progenitor cells,– clinical trials in the US depended on developing ex vivo culture and expansion techniques that satisfy FDA requirements for human trials. Recently, the first human trial using ESC-derived cells was approved by the FDA for acute spinal cord injury (http://www.geron.com/). For the rest of this chapter, we focus on adult hematopoietic stem cell sources in current clinical transplant trials for multiple sclerosis (MS). Adult stem cells are obtained from differentiated tissue compartments during or after birth, and are lineage-restricted (multipotent) to differentiate into and replenish a particular tissue or organ system. Most adult stem cells are difficult to collect safely in clinically relevant numbers. For example, neuronal stem cells are located in the periventricular area of the brain while liver stem cells (ovalocytes) are located in the periductal area of the liver parenchyma, making harvest in a living patient impractical. In contrast, hematopoietic stem cells (HSCs) may be easily and safely collected in clinically significant number from the bone marrow, blood, or placenta (umbilical cord blood, UCB). For UCB, safe and rapid engraftment, following myeloablative (marrow ablative) therapy, depends on infusion of more than 2.5 × 10 mononuclear cells/kg of recipient weight (Cord Blood Registry Guidelines), which limits the use of UCB to children, although some centers infuse multiple UCB units from different deliveries to achieve sufficient HSCs for adult recipients. In adults, HSCs are generally collected from the blood, and termed peripheral blood stem cells (PBSCs).
ASJC Scopus subject areas