Optimizing autologous cell grafts to improve stem cell gene therapy Nikoletta Psatha, Garyfalia Karponi, Evangelia Yannaki  Experimental Hematology  Volume 44, Issue 7, Pages 528-539 (July 2016) DOI: 10.1016/j.exphem.2016.04.007 Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Figure 1 Approaches to optimization of autologous gene-engineered cell grafts. (i) Mobilization with agents yielding leukapheresis products highly enriched in HSCPs. (ii) CD34+ cell enrichment or further purification of the most “stem cell”–like HSPCs to reduce the number of cells for genetic modification and increase the chance of high-in-the-hierarchy HSCs to be targeted by the vector. (iii, iv) Expansion of the transduced cells with preservation of their stemness phenotype by co-culture of the graft with feeder cells or pretreatment of the gene-modified cells with factors that control intrinsic cell proliferation pathways or small molecules that allow cell division but prevent differentiation. (v) Priming of the transduced cells with effector molecules that improve engraftment on transplantation, providing fast reconstitution and in vivo long-term persistence of the genetically modified cells. Experimental Hematology 2016 44, 528-539DOI: (10.1016/j.exphem.2016.04.007) Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions