Approaches to Hematopoietic Stem Cell Separation and Expansion

This chapter focuses on strategies for identification and separation of human hemopoietic stem cells (HSCs) and lineage-committed progenitors. It also discusses approaches to HSC expansion and recent clinical experience with ex vivo manipulated hemopoietic cells. During the last decade, there has been great interest in the development of methods for manipulating the growth and development of human HSCs and progenitor stem cells for therapy. These initiatives include the generation of committed progenitor cells and myeloid precursors for transplantation, expansion of HSCs from hemopoietic tissues, such as umbilical cord blood (CB) to increase safety and applicability of hemopoietic cell transplantation, and the use of HSCs as vehicles for gene therapy. Optimal methods for manipulating human HSCs and their progeny for any therapeutic application will arise from a comprehensive understanding of the molecular regulatory mechanisms that control stem cell fate and hemopoietic cell differentiation. Even though it is well recognized that the hemopoietic microenvironment plays a key role in these processes, the exact molecules responsible for these noncell autonomous aspects of HSC regulation remain to be elucidated. Accordingly, a major challenge for the field is to define the molecular “parts lists” for both stem and progenitor cell populations and the supporting microenvironment and moreover, to establish how these individual components interact to form regulatory pathways and networks.