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Research
Our current research objectives are designed to address four areas of complexities both in applied therapeutics and in basic biomedical sciences.
Studying stem and progenitor cell behavior in 3D environments and developing new approaches for high-throughput production of therapeutic cells. We have recently published (Tissue Engineering, Jan-Feb, 2005) studies on ES cell hematopoiesis within scaffold structures under both static and dynamic culture conditions and demonstrated that compared to state-of-the-art 2D cultures, 3D environments and specifically dynamic, bioreactor-based cultures provide significantly enhanced hematopoietic differentiation of ES cells. We further demonstrated that hematopoietic progenitor cells, derived from ES cells in such 3D environments can be successfully directed into the dendritic cell lineage. Such strategies can be eventually used to generate, in 3D bioreactors, large numbers of therapeutic hematopoietic progenitors for transplantation therapy, or dendritic cells for cancer immunotherapy. This work has recently received significant attention, as it was the first to show ES cell behavior under static and dynamic bioreactor cultures and there effect on hematopoietic differentiation. The paper was showcased at the journal website and was made feely available to all. We have also submitted a follow up manuscript describing our results in comprehensive gene expression analysis of these cells using extensive cDNA microarray studies. Our results identify a series of genes that are regulated in ES cells cultured in 2D versus 3D (static or dynamic) environments and clearly indicate that cell adhesion, apoptosis and certain signal transduction pathways are important contributors of stem cell differentiation in 3D. The second project in this direction involves creating functionalized biomaterials that can trigger notch signaling, a key event in lymphopoeisis from progenitor cells. Our overall goal here is to develop technology that can produce therapeutic T cells from stem cells using notch-signaling biomaterials. We have recently reported successful generation of T cell using magnetic microbeads functionalized with the notch-ligand DLL4. This is the first report in which T cells have been obtained in a purely synthetic system with only paracrine presence of stromal cells. Such concepts should eventually allow us to produce T cells in a high-throughput manner in bioreactor type cultures. The University has filed for provisional patent application for this technology. References
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The second major initiative in stem cell research in the lab is to develop
engineering concepts to understand the fundamental interactions of stem and
progenitor cells with biomaterial environments and engineer new methods for
producing therapeutic progenitor cells with high efficiency. This effort has
developed into two major projects: first, culture of embryonic stem (ES) cells
in static or dynamic 3D environments in order to understand cell behavior and
gene expression changes under various environmental conditions and secondly,
differentiation of adult and embryonic stem cells to therapeutic T cell lineages
using biomaterial-induced notch-signaling. |
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