Embryonic Stem Cells Go Dopaminergic

muscle dystrophin expression (Gussoni et al., 1999). The Our limited life expectancy, and inevitable death, is origin of the adult stem cells is not known. They may be brought about by the ongoing deterioration of the body’s residual undifferentiated embryonic cells or, as recent essential cell types, tissues, and organs. Thus, either a evidence suggests, committed/differentiated adult cells reliable source of replacement organs or cells or a that reacquire multipotency in response to environmenmethod to continually induce the repair of endogental signals. For example, oligodendrocyte precursor ous organs would profoundly affect the current statistics cells that normally give rise only to oligodendrocytes of aging-related disease and death. The prospect of can became multipotent neuronal stem cells following greater longevity, associated with an increased expecsequential exposure to PDGF, bFGF, and BMP2&4 tancy of good health, underlies the intense excitement (Kondo and Raff, 2000). surrounding work on embryonic stem cells. Stem cells The ability of stem cells to provide us with better are unique in that they have the capacity for unlimited health and longevity is dependent on our ability to idenself-renewal along with the ability to produce multiple tify the extracellular factors that direct the differentiation different types of terminally differentiated descendants. of stem cells to a desired lineage. However, most of the Thus, they might serve as a multipotential source of signals that instruct embryonic or adult stem cells to replacement body parts in cardiovascular, autoimmune, differentiate to a specific lineage have not yet been idenAlzheimer’s, or Parkinson’s disease or for diabetes, ostified, and thus the resultant ES cell progeny cannot be teoporosis, cancer, spinal cord injury, or birth defects. controlled. Only recently have efforts to identify such Identifying the extrinsic signals that control lineage spefactors begun to bear fruit, and last year a group was cific differentiation of stem cells to allow the generation able to induce ES cells to differentiate to oligodenof specific tissues in vitro and, eventually in vivo, is a drocytes and astrocytes in vitro with a high frequency, critical issue in stem cell research. by sequential exposure to FGF2, EGF, and PDGF. When Embryonic and Adult Stem Cells transplanted into rats lacking endogenous myelin proHave a Lot of Potential ducing oligodendrocytes, the ES-derived glial precursor Stem cells are a major component of the early embryo, cells differentiated to functional oligodendrocytes, which but also exist in many adult tissues. Embryonic stem were able to myelinate axons in the brain and spinal (ES) cells are derived from the inner cell mass of the cord (Liu et al., 2000). Similarly, another group showed embryonic blastula, and this small group of cells (13 at that the exposure of ES cells to retinoic acid prompted the 64 cell stage embryo) will normally give rise to the them to produce glutaminergic, GABAergic, and glyentire embryonic yolk sac, the allantois, and the amnion. cinergic neurons (Gottlieb and Huettner, 1999) that, ES cells can be maintained indefinitely as pluripotent when transplanted into the rat spinal cord 9 days after stem cells in tissue culture. However, when injected into a traumatic injury, elicited partial functional recovery the blastocyst of a host mouse embryo, the donor ES (McDonald et al., 1999). cells integrate into the host inner cell mass and give rise Possible Utility in Parkinson’s Disease to descendants in all tissues of the resulting chimeric Identifying the conditions required for neural cell inducoffspring, including germ cells. When injected under the tion of ES cells may be particularly useful for the treatskin of an adult nude mouse or grown without essential ment of a progressive neurodegenerative disorder such growth factors in vitro, ES cells give rise to a random as Parkinson’s disease. Parkinson’s disease (PD), which collection of differentiated cells and tissues including afflicts over a 1 million people in the US, is characterized heart, muscle, blood islands, neurons, pigmented cells, by the degeneration and death of midbrain neurons that macrophages, epithelia, and adipocytes. produce the neurotransmitter dopamine, resulting in Whereas embryonic stem cells are transient, adult tremors at rest, an inability to initiate or complete routine stem cells appear to reside permanently in most tissues, movements, muscle rigidity, postural instability, and including the brain, bone marrow stroma, liver, skin, and lack of facial expression. Transplantation of dopaminermuscle. Adult stem cells were initially thought to be gic neurons (DA neurons) taken from human fetuses into limited in their developmental potential to the regeneraPD patients shows a remarkable, yet inconsistent, ability tion of cell types comprising their tissues of origin. Howto replace endogenous degenerating DA neurons and ever, in a recent study, stem cells from the adult brain to ameliorate some of the disease symptoms (Bjorklund