(232e) Implantable Microenvironments for Stem Cell and Cancer Research

Bone marrow provides unique microenvironments for hematopoietic stem cells. It is also known as a major reservoir for many circulating tumor cells and may represent a constant source of metastatic cells that lay dormant and disseminate from the marrow. However, inaccessibility of the bone marrow space has limited systemic investigation of these vital cellular processes in normal and pathological settings. In this presentation, we will introduce implantable humanized stem cell niche that can support hematopoietic progenitor cells in an accessible, ectopic site under the skin. The implants consist of human bone marrow stroma cells seeded in a 3D microfabricated biomaterial that mimics the physical and anatomical features of the bone marrow. When implanted subcutaneously in immunocompromised mice, these stromal cell-laden biomaterials formed a highly vascularized and organized marrow-like tissue over a period of time. These constructs represent 2% of the native marrow volume and recruited host Lin-Sca-1+c-kit+ hematopoietic progenitor cells to the site at 20% of normalized marrow levels. We demonstrated that intravenously injected human CD34+ progenitor cells and human leukemic cells were spontaneously recruited to the implanted microenvironments. Microenvironment dependent tumor metastasis was also modeled generating an orthotropic tumor that shed circulating tumor cells into the bloodstream. Finally we employed genetically engineered stromal cells that synthesis specific human cytokines to determine cytokine dependent human CD34+ cell behaviors. We envision that implantable and tunable marrow-mimicking tissue microenvironments could enable various aspects basic and translational stem cell and cancer research.