*** 9800926 Pykett This Small Business Innovation Research Phase II project will extend the development of Cellfoam hematopoietic stem cell (HSC) culture systems for long-term maintenance aimed at advancing bone marrow transplantation and HSC gene therapy procedures. Phase I research demonstrated the ability of Cellfoam to maintain and expand primitive, multipotent HSCs for extended periods in an environment in which no supplemented cytokines are required. Building on the proof of principle established in Phase I research, Phase II will develop advanced Cellfoam applications by addressing the following specific aims: Pre-clinical optimization of large scale Cellfoam-HSC culture systems; Evaluation of the in vivo engraftment capabilities of HSCs cultured in large scale Cellfoam systems using a SCID mouse animal model; Examination of transduction rates and in vivo engraftment capabilities of HSCs transduced in large scale Cellfoam systems. This work will demonstrate the ability of Cellfoam to promote, on a clinically relevant scale, the extended survival, expansion and transduction of multipotent HSCs in a cytokine-free system for enhanced bone marrow transplantation and gene therapy, goals which are currently not possible with existing technologies and which would markedly enhance the ability to treat individuals with various hematopoietic disorders. Commercial applications are aimed at clinical markets for bone marrow transplantation and gene therapy of hematopoietic disorders. The annual US market for bone marrow transplantation stands at $4.5 billion; markets for HSC gene therapy are just emerging. ***