Combined positive negative selection in stem cell transplantation: Perspectives in graft engineering

Background: Manipulation of hematopoietic stem cell grafts has become a ver y exciting research area due to the improved accessibility of hematopoietic progenitor cells using apheresis procedures compared to that of bone marro w harvesting. This development in graft engineering relates also the furthe r refined approaches to eliminate contaminating tumor cells from autografts or to expand hematopoietic progenitors and postprogenitor cells ex vivo. F urthermore, manipulation of stem cell grafts in the allogeneic setting aims at the separation of graft versus leukemia(GVL)- and graft versus host(GVH )reactive cells, selection of graft-facilitating cells, and tolerance-induc ing cells. This study focuses on recent advances in the field of graft engi neering with respect to the combination of positive and negative cell selec tion. Materials and Methods: The selection procedures in use rely either on the positive selection (i.e. enrichment) of a given target cell population using either immunoaffinity approaches or density gradient centrifugation procedures. Negative selection methods (i.e. depletion of unwanted cells, e .g. tumor cells, GVH-reactive cells) also utilize immunoaffinity approaches . Furthermore, cell depletion can be achieved by pharmacological agents, ce ll-specific induction of apoptosis, or genetic cell manipulation. Results: Using combined positive and negative se lection, a 4 to > 6 log depletion o f unwanted cells (i.e. tumor cells or T cells) from stem cell products can be achieved. Conclusion: Due to recent developments in stem cell collection and graft en gineering, custom-tailored cellular therapy is becoming a reality in the se tting of autologous and allogeneic stem cell transplantation.