Abstract This project will develop and verify a microtissue engineered bioreactor platform to expand bone marrow cancer stem cells and create xenograft models using frozen MDS patient marrow cells. The project specific aims are: (1) Specific Aim 1: Microfluidic bioreactor for human HSC expansion from a low volume marrow sample; (2) Specific Aim 2: Genetically engineered scaffolds to recreate a MDS microenvironment ex vivo; and (3) Specific Aim 3: Ex vivo differentiation testing of MDS stem cells to predict leukemic transformation. The deliverable of the project will be a qualified bioreactor culture system and protocol to expand rare cells, such as pre-leukemic stem cells, from a small volume bone marrow biopsy tissue sample for use in prospective clinical trials.