Stem cell selection: cornerstone to advanced cell processing for transplantation

CD34 is a cell surface glycoprotein present on hematopoietic stem cells and progenitors. Recently techniques to markedly enrich for CD34 positive cells have been developed which have greatly facilitated clinical research in allogeneic and autologous transplantation. Blood and marrow transplantation (BMT)requires administration of adequate numbers of stem and progenitor cells to restore hematopoiesis. The mature elements of the marrow do not contribute to engraftment and the CD34 positive fraction is capable of fully restoring lymphohematopoiesis. Positive selection of CD34 positive stem and progenitor cells can be achieved using a number of systems employing antibodies to CD34 and isolation of the bound cell fraction, eliminating CD34- cells from the transplant graft. CD34 selection has a number of practical advantages for auto and allo transplantation; it reduces the cell number by 99%, reducing the volume of cells stored and the amount of the cryoprotectant DMSO which is ultimately administered. This, in turn, reduces the symptomatic toxicity of the infusion. Most malignant cells do not express CD34, and CD34 selection eliminates malignant cells; available devices result in a 2-3 log reduction and can be combined with a second antibody mediated depletion step to more thoroughly tumor cells giving an additive purging effect. Similar considerations hold for Tcells from allografts to reduce GVHD. CD34 selection is critical for many rapidly sophisticated areas of clinical research, including gene therapy in which purified stem and progenitors cells are transduced and ex vivo expansion, in which hematopoietic stem and progenitor cells are stimulated to proliferate in vitro.