This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To generate iPS cells from SLE patients and use them as a scalable source of autologous primitive hematopoietic cells for transplantation, as well as regulatory dendritic (DC) and T cells for immunotherapy in Lupus patients. Induced pluripotent stem (iPS) cells are stem cells artificially derived from somatic fibroblasts through insertion of certain genes critical for the maintenance of pluripotency of human embryonic stem (hES) cells. It has been shown that these cells behave similar to hES cells, i.e. capable of self-renewal and large-scale expansion and differentiation toward all three germ layers. Our idea is that iPS cells can be generated from SLE patients and used as a scalable source of autologous primitive hematopoietic cells for transplantation, as well as regulatory dendritic (DC) and T cells for immunotherapy. Because iPS cells are similar to hES cells, they can be sustainably expanded and genetically altered in a highly controlled way that is not yet possible with more committed HSCs. Thus, iPS cells could provide important advantages over somatic HSCs as target cells for stem cell based therapy of SLE. In this application we propose to identify cell subpopulations and conditions essential for generation of engraftable hematopoietic cells, T cells and DC from iPS cells. This project was funded in Fall 2008 and has just begun.