ABSTRACT
Stem cells are defined as undifferentiated cells that can proliferate and have the capacity of both self-renewal and differentiation. Most adult tissues have multipotential stem cells that are capable of producing a limited range of differentiated cell lineages appropriate to their location. Likewise, recent evidence suggests that stem cells of some tissues can give rise to differentiated cells of distinct tissues under certain circumstances. Therefore, stem cells provide a theoretically inexhaustible supply of cells with potential to replace tissues under conditions where age, disease or trauma has led to tissue damage or dysfunction. Specifically, stem cells offer great promise for tissue regeneration, cell-based transplantation therapies and gene therapy protocols. However, since the stem cell frequency in most adult tissues is rare, potential clinical applications will require the ability to expand stem cells ex vivo or in vivo. Most of the research regarding stem cell expansion has been done on hematopoietic stem cells. To date, no studies have demonstrated convincing data that the true multipotential hematopoietic stem cell can be expanded ex vivo without coincident induction of differentiation and generation of committed progenitor cells. Once differentiated, the progenitor cells acquire tissue-specific functional properties and the self-renewal properties of the stem cell population are lost. Since hematopoietic stem cells appear to have unlimited self-renewal properties in vivo, this suggests that the ex vivo culture conditions used to date are not representative of the in vivo conditions that support stem cell self-renewal. Recent studies described later in this chapter, have made great strides toward defining the genes, culture conditions and cell to cell interactions responsible for self-renewal. Through continued investigation it is anticipated that stem cell expansion ex vivo will be achievable.
