Chapter 4: Hematopoietic Stem Cells and their Role in Regenerative Medicine

Hematopoietic stem cells (HSC) are the building blocks of the blood-cell forming (hematopoietic) system. They are endowed with the potentials of self renewal, proliferation and differentiation into all the blood cell lineages, and thus provide the system the capacity to maintain a constant number of mature functional cells under changing physiological conditions. Although they have no morphological distinctive features, they can be identified by flow cytometry based on their unique expression of surface antigens. The expression of CD34 (or CD133) and lack of expression of lineage-specific antigens allow their purification by cell sorting flow cytometry or immuno-magnetic bead separation. Transplantation of HSC is a well-established clinical practice. It is most often performed for patients with hematological and immunological diseases or with certain types of cancers. Sources of HSC for transplantation include bone marrow, peripheral blood (following immobilization and collection of the HSC) and neonatal umbilical cord blood. The number of available HSC poses a significant problem in particular for transplantation of cord blood cells into adults. Several protocols have been devised to increase the number of HSC, including co-transplantation of several units and ex-vivo expansion of HSC. Their proliferation depends on several hematopoietic factors (cytokines) and/or co-culture with stromal cells. The expansion HSC and the maintenance of their stem cell properties are limited by cell differentiation and apoptosis. We devised several strategies to overcome this problem, including the addition of the copper-chelator tetraethylenepentamine. The efficient ex-vivo manipulation of HSC is still an unsolved objective. Success in this field will provide the means for expansion of HSC as well as more differentiated progenitors for transplantation of donor's cells as well as for gene therapy using autologous cells. In light of the recent discoveries of the plasticity of HSC to give rise to non-hematopoietic cells, in vitro manipulated HSC may offer new horizons for regenerative medicine.