Improving Techniques for Cell Implantation and their Impact on Managing Diseases of the Pancreas

• Author / Creator

  Abualhassan, Nasser

• The use of experimental animals early in the twentieth century has revolutionized medicine and significantly improved our understanding of disease processes. The ability to reproduce a medical condition in a mouse model has provided great insights into the cellular and molecular biology of the disease process and a valuable medium to develop and test therapy that would eventually be translated into the clinic. Cell implantation has been utilized extensively in cancer research and has resulted in remarkable progress in cancer therapy especially in leukemia. Cellular transplantation has also proven valuable as a replacement therapy such as in type 1 diabetes. A major barrier to successfully translate the observation in a mouse model to the clinic is the ability to generate a relevant mouse model that accurately represents the clinical condition of interest. The objective of this graduate work is to study the existing cellular implantation animal models in an attempt to modify and improve the techniques used for cellular implantation. In the first part of this thesis, we utilized a novel prevascularized subcutaneous site, developed in our laboratory, for pancreatic cancer xenograft. This approach accelerated tumor growth in our immunodeficient mouse model, which would have a great clinical value when implemented in personalized medicine. Taking advantage of the accelerated tumor growth, characterization and drug testing of the tumor can be done in time to direct therapy in the clinic for individual patients. In the second part of this thesis, we have utilized a novel transplantation method for pancreatic islet transplantation to treat diabetes. In this method, islets are seeded on micro organ-derived scaffolds and subsequently implanted into the peritoneal cavity of immunodeficient mice. This approach restores the islet microenvironment by providing a wide variety of extracellular matrix proteins that resulted in a significant reduction of the required islet mass in an extravascular site. This could be of a great clinical value given the potential of transplanting more than one recipient with one donor organ.

• Subjects / Keywords

  • Cancer xenograft
  • Pancreatic cancer
  • Islet transplantation

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3W08WN1Q

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.