In recent years, great advances have been made in the field of stem cell differentiation. Seminal insights in the area of developmental biology and tissue regeneration have made ex vivo differentiated cells a realistic alternative for transplantation applications. The recent application of these murine-based insights to human systems has paved new paths in autoimmune disease, chemotherapy, and immuno-deficiency research. Such strides would eliminate the hurdles associated with adoptive transfer including limited availability of transplantable cells, site morbidity, difficulties in cell isolation and expansion lag time. Current approaches in ex vivo hematopoiesis and T cell differentiation have begun to explore the effects of biomaterials on differentiation efficiency. These approaches, however, have not fully studied the quantitative effects of biomaterials and their properties on hematopoietic and T cell differentiation generation. Our goal was to design biomaterials whose properties could be tailored to improve differentiation efficiencies in T cell differentiation. Our work is dedicated to fabricating and characterizing Notch ligand functionalized microbeads for T cell differentiation applications. Our work has shown stable functionalization of Notch ligands on microbeads that can be quantitatively varied to achieve optimal Notch signaling. We have also demonstrated limited cellular toxicity and effective Notch signaling upon exposure to Notch ligand functionalized beads. Finally, we have successfully differentiated T cell progenitors from hematopoietic stem cells using the functionalized microbeads. As a side study, we have fabricated and characterized polymeric PLA scaffolds that were systematically varied and studied for their effects on hematopoietic differentiation efficiency. Insights gained from these studies should provide a better understanding of the microenvironmental signals in hematopoiesis and aid in the development of efficient technologies for the production of hematopoietic progenitors and T cells for therapeutic applications.
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/3648 |
| Date | 29 August 2008 |
| Creators | Taqvi, Sabia Zehra, 1980- |
| Contributors | Roy, Krishnendu |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | electronic |
| Rights | Copyright © is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works. |
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