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Human Endothelial Progenitor Cells: A Novel and Promising Cellular Therapy For Regenerative Medicine
AuthorWood, Joshua Alan
Biochemistry and Molecular Biology
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Endothelial progenitor cells represent a novel and promising therapy for a myriad of tissues and conditions including diseases and disorders of the liver and small intestine. Cirrhosis and other diseases have created a need for a readily available supply of hepatocytes and supporting cells in diseased and scarred liver. Following chemo/radiation therapy and inflammatory bowel disease, the cell populations of the small intestine are diminished and a cell therapy for the replenishment of these populations is needed. Additionally, the cellular makers to identify both EPCs and mesenchymal stem cells (MSCs) have been defined in the literature but a debate remains as to the heterogenic vs. homogenic nature of the cell populations. This dissertation investigates the engraftment potential of EPCs in the liver when transplanted (Tx) In Utero into the pre-immune sheep model via two routes of injection, Intra-hepatic (IH) and Intra-peritoneal (IP). Upon finding engraftment, the contribution of these cells to vasculature and parenchymal tissue as well as their differentiative potential in contribution to the developing liver was investigated. Tx EPCs engraft albeit at low levels but preferentially associate with vasculature. In addition to their association with vasculature, the EPCs maintain the expression of endothelial markers in addition to expressing markers raging from fully differentiated hepatic cells to liver stem cells. In addition to their contribution to the liver, EPCs not only engraft into the small intestine but do so in a preferential manner in the area containing the crypts of Lieberkühn (above the muscularis mucosa and below the crypt-villus junction). Upon transplantation, these cells actively engraft and differentiate into both intestinal stem cells (ISCs) and into the supporting cell types of the ISC niche as well as mature cells of the intestinal parenchyma. Finally, LAM-PCR and LM-PCR were employed to identify vector integration sites in both MSCs and EPCs transfected with a variety of retroviruses. These experiments are designed to address the existence of a heterogeneous or homogenous population in both the EPC and MSC populations. Further testing on an experimental sample reveals the presence of chimeric DNA in the sample and successful amplification of integration sites in this sample is pending further investigation.