Detection and Identification of Tissue Stem Cells: Tracking an Elusive Prey

This chapter discusses the process of detection and identificatin of tissue stem cell. Unlike most cell types, stem cells are defined by virtue of their functional characteristics. Essentially, "a stem cell is as a stem cell does." This concept, while accurate, does little to help an unseasoned investigator determine whether they have identified a stem cell or not. Moreover, the use of a functional definition imposes a biological version of the Heisenberg uncertainty principle, as in order to determine whether a stem cell has been isolated, one must manipulate it experimentally, which will almost certainly alter its properties. This degree of ambiguity makes the identification and characterization of tissue stem cells a nontrivial task, and has resulted in heated debates between research groups. For a cell to be considered a bona fide stem cell, it must demonstrate a significant proliferative capacity, maintain itself over an extended period of time, and be able to the generate a large number of differentiated progeny and regenerate the tissue from which it was derived. While the last property cannot be demonstrated in vitro, one can contend that faithful adherence to this definition is essential for insight into the biology of stem and progenitor cells, as this is the only means by which to differentiate these two populations. In regard to this, an enabling and robust readout of stem cell activity is absolutely essential. This has typically been achieved by employing an in vitro assay system (such as the neurosphere assay); although in vivo methodologies such as serial transplantation have also proven sufficient in the case of hematopoietic stem cell.