happens to them in culture (in vitro). For example, Ron McKay described how precursor cells taken from the mouse midbrain can be cultured in vitro to generate cells that appear to be dopaminergic neurons, but only for a very short time. (Dopaminergic neurons produce the chemical mediator L-dopa and are depleted in patients with Parkinson’s disease.) Recalling that it is well known that the spinal cord generates motor neurons in response to signals that come from other tissues, McKay suggested that the capability of the precursors of the midbrain to make dopaminergic neurons might be transient in culture because they require stimulation from signals present only in the brain.

A third problem in understanding the capabilities of adult stem cells is the relationship of the cellular environment to the concept of plasticity in adult stem cells. Markus Grompe showed that HSCs and pancreatic stem cells can give rise to liver cells called hepatocytes that will repopulate a diseased mouse liver, demonstrating the plasticity of adult stem cells. However, in his experiment, HSCs and pancreatic stem cells were very inefficient in repopulating the liver relative to the ability of transplanted hepatocytes themselves. This could mean that the plasticity of adult stem cells is a marginal capacity that can be exploited only with a much greater understanding of the environmental signals that influence adult stem cells. No one knows what steps HSCs or pancreatic cells go through in generating a hepatocyte, or what signals cause them to migrate to the liver in the first place. Moreover, some of the apparent plasticity in adult stem cells is difficult to interpret because it has been accomplished in abnormal environments, for example, in mice that are immunologically impaired (Mezey et al., 2000) or sublethally irradiated (Brazelton et al., 2000).

Fourth, a major weakness of stem cell research asserted by Grompe is that most studies inadequately demonstrate that stem cells have produced a functionally useful cell in the organ. Most studies showing the plasticity of stem cells rely on the detection of proteins in the newly generated tissues that are commonly associated with a particular type of differentiated cell. But there is no consensus in the scientific community that the detection of a particular protein constitutes sufficient evidence that the



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