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Monitoring Stem Cell Research 
presence or absence of CD34, has yielded mixed results in terms of 
the identification of putative stem cells. There is evidence that the 
expression of CD34 and CD133 can actually change over time, and its 
expression may be part of a cycling phenomenon among human 
hematopoietic and mesenchymal stem cells in the bone marrow and 
peripheral blood, and perhaps in other tissues,® f.e., an isolated 
CD34^ cell may become CD34’, and then reacquire CD34 expression. 
Likewise, a systematic analysis of the cell surface markers and 
differentiation potential of supposedly distinct isolated populations 
of human bone marrow stem cells revealed no differences in practice 
between the cell populations.^® Moreover, an analysis of genetic and 
ultrastructural characteristics of human mesenchymal stem cells 
undergoing differentiation and dedifferentiation has revealed 
reversibility in the characteristics studied.” Thus, any attempt to 
isolate a single type of adult stem cell for study may not actually 
capture the intended cell, or may, by using a particular set of 
isolation or growth conditions, alter its gene expression. This idea 
has been elaborated by Thiese and Krause, who note that this 
"uncertainty principle" means any attempt to isolate and 
characterize a cell necessarily alters its environment, and thereby 
potentially its gene expression, identity, and potential ability to 
differentiate along various lineages. Likewise, the stochastic nature 
of cell differentiation in such dynamic and interacting systems means 
that attempts to delineate differentiation pathways must include 
descriptions of each parameter associated with the conditions used, 
and still may lead only to a probabilistic outcome for differentiation of 
a stem cell into a particular tissue. Blau et ai.'® have raised the 
question of whether there may be a "universal" adult stem cell, 
residing in multiple tissues and activated dependent on cellular 
signals, e.g., tissue injury. When recruited to a tissue, the stem cell 
would take its cues from the local tissue milieu in which it finds itself 
(including the soluble growth factors, extracellular matrix, and cell- 
cell contacts.) Examples of such environmental influences on fate 
choice have been noted previously.” Thus, it may not be surprising 
to see examples of cells isolated using the same marker set showing 
disparate differentiative potentials,^®””'” based on the context of 
the isolation or experimental conditions, or to see cells with different 
marker sets showing similar differentiation. In the final analysis, 
description of a "stem cell", its actual tissue of origin, and even its 
differentiation ability, may be a moving target describable only 
within the context of the particular experimental paradigm used, and 
may require asking the correct questions in context of the cell's 
identity and abilities not clonally but rather within a population of 
cells, and within a certain environment.”'” 
PRE-PUBLICATION VERSION 
