Abstract
Background: Manipulation of hematopoietic stem cell grafts has become a very exciting research area due to the improved accessibility of hematopoietic progenitor cells using apheresis procedures compared to that of bone marrow harvesting. This development in graft engineering relates also the further refined approaches to eliminate contaminating tumor cells from autografts or to expand hematopoietic progenitors and postprogenitor cells ex vivo. Furthermore, 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-inducing cells. This study focuses on recent advances in the field of graft engineering with respect to the combination of positive and negative cell selection. 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, cell-specific induction of apoptosis, or genetic cell manipula-tion. Results: Using combined positive and negative selection, a 4 to > 6 log depletion of 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 engineering, custom-tailored cellular therapy is becoming a reality in the setting of autologous and allogeneic stem cell transplantation.
Published Version
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