Embryonic stem cells are pluripotent cells that have the ability to differentiate into cell lineages from all three germ layers. However, the use of stem cells in therapeutics relies on the ability to control their differentiation. Studies have shown that implantation of undifferentiated ES cells into an injury site leads to their spontaneous differentiation and potential tumor formation. One method to control stem cell differentiation is through the design of biomaterials that mimic the natural microenvironment during development. Biomaterials can provide a microenvironment in which host as well as replacement therapeutic cells can reside. Controlling this microenvironment provides opportunities to present specific physical and soluble cues that control cell and tissue fate. Herein, we conjugate the cell adhesion molecule L1 to type I collagen to allow for its sustained, physiologically relevant presentation. L1 is a member of the immunoglobulin superfamily shared by neural and immune cells and has been shown to promote neurite extension as well as functional recovery in adult rats after contusion-induced spinal cord injury. In this study, we will investigate the role of L1 on mouse embryonic stem cells. We will assay the effects of L1 presentation on cell adhesion, proliferation, and most importantly differentiation of embryonic stem cells (mESCs). As L1 has a homophilic binding domain, we will study the effects of using a genetically modified mESCs that overexpress L1 in combination with our L1-grafted biomaterial. Collectively, these studies will provide greater insight into the role of designing materials to guide the differentiation of stem cells. These materials may be used as delivery mechanisms for stem cell therapeutics or scaffolds on which ones own stem cells can differentiate towards a particular required cell type or lineage.
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Biomedical Engineering
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Rutgers University Electronic Theses and Dissertations
Rutgers University. Graduate School - New Brunswick
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