We propose a multidisciplinary program, focusing on the development of novel approaches for directing the differentiation, proliferation and tissue-tropism of specific hematopoietic lineages, using micro- and nano-fabricated cell chips. We will use advanced nanofabricated surfaces functionalized with specific biomolecules, and microfluidics cell chips to specify and expend regulatory immune cells for treating diverse inflammatory and autoimmune disorders in an organ- and antigen-specific manner. The proposed cell-chip will create ex-vivo microenvironments mimicking in-vivo cell-cell interactions and molecular signals involved in differentiation and proliferation of hematopoietic cells. Cell chip development and optimization will be supported by high throughput microscopy to select for optimal conditions. “Educated” cells will be employed for in vivo experiments in mice and the methodology will be further adapted for human cell populations, and applied for clinical diagnosis and therapy as well as the developments of clinically-relevant devices. Regulatory T-cells are extremely promising cells for treatment of inflammatory and auto-immune disease, as well as for tolerance induction in organ transplantation. To be effective they must be produced conveniently, at large numbers with an optimally tuned phenotype. The methodology is suggested to overcome current obstacles in obtaining therapeutically significant numbers of T cells. We propose to apply the suggested methodology for treating different inflammatory or autoimmune diseases including type-1 diabetes using targeted immunotherapeutic approaches. Developing new methods for producing large numbers of finely-tuned and tissue-targeted regulatory cells will make this approach clinically viable. This novel methodology can be extended to directing differentiation of other specific T-cell and hematopoietic lineages, with possible applications for targeting other autoimmune diseases and treating tumors or graft rejection.