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.
An engineered bone marrow stem cell bioreactor is proposed that continuously perfuses a 3D hydrogel scaffold for low volume marrow biopsy studies. The scaffold is customized to mimic a bone marrow cancer microenvironment by using genetically engineered stromal cells with the objective to expand pre- leukemic cells from patient bone marrow samples (which cannot otherwise grow ex vivo or in mouse xenografts) using this bioreactor system. Patient MDS cells grown in the scaffold will be tested for ex vivo growth and results will be correlated to patient outcomes as a companion model. This research can pave the way for immediate applications in prospective, companion clinical trials in MDS patients as well as using this small volume bioreactor platform for other rare bone marrow cells.
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