Type of Document Thesis Author He, Yang Author's Email Address firstname.lastname@example.org URN etd-11122004-102425 Title Applications Of Small Intestine Submucosa In Tumor Model And Vascular Tissue Engineering Degree Master of Science Department Chemical Engineering, Department of Advisory Committee
Advisor Name Title Teng Ma Committee Chair Bruce R. Locke Committee Member Chi-Kai (Kevin) Chen Committee Member Keywords
- Small Intestine Submucosa (SIS)
- Vascular Graft
- Human Breast Cancer cell
- Tumor Model
- Human Umbilical Vein Endothelial Cell
Date of Defense 2004-11-02 Availability unrestricted AbstractSmall intestinal submucosa (SIS) is an extracellular matrix (ECM) harvested from pig. It contains primarily collagen with multiple proteins and growth factors. It is a biocompatible scaffold that supports cell growth in vitro and can be remodeled by the host after transplantation. The goal of this study was to use SIS to establish a tumor model and an endothelialized vascular graft.
To establish a tumor model, human breast cancer cells were grown on SIS. Similar to carcinoma in situ and tumor invasion, cancer cells in the tumor model grew and migrated into SIS matrix, and a high percentage of proliferating cells was shown on the SIS surface compared to the SIS interior. To simulate tumor angiogenesis, the establishment of a co-culture model with human umbilical vein endothelial cell (HUVEC) and human breast cancer cell was tried. The glucose in medium was consumed by the cancer cells and the HUVEC could not achieve an adequate density, suggesting that a bioreactor, which could supply consistent nutrient environment for HUVEC is necessary for the further angiogenesis modeling.
Endothelialization of the luminal surface of small-diameter vascular graft is a promising method to avoid occlusion of the prosthese. The results of this study clearly demonstrated that SIS supported HUVEC proliferating and endothelial cell growth factor suppliments (ECGS) up-regulated the proliferation rate. The proliferation rate of HUVEC on SIS showed three phases including quiescent, proliferation and confluence phase. In confluence phase, an intact endothelium monolayer was formed, and CD31, an adhesion molecule expressed by HUVEC concentrated on the borders of the adjacent cells. ECM was secreted by HUVEC and anchored HUVEC onto SIS. For in vivo condition, oxygen tension is about 5%, which is defined as hypoxia comparing to 20.8% oxygen tension for in vitro cell culture. Experiments showed that HUVEC on SIS could survive and show a higher viability under hypoxic condition.
These findings should help guide the future study of SIS applications in tumor models and small-diameter vascular grafts.
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