[Truncated abstract] Malignant mesothelioma (MM) is an aggressive primary tumour of the serosa, reported to be derived from transformation of mesothelial cells and associated with past exposure to asbestos. MM is typically classified into three major subtypes based on histological features, however it has been documented that MM tumours also contain other tissue types. For example, MM tumours have been reported to contain areas of osseous and/or cartilaginous tissue. It has been proposed that these unusual MM variants may result due to the capacity of cells of mesothelial origin to differentiate into multiple cell lineages. Serosal calcification and pleural plaques have also been attributed to abnormal healing of the mesothelium and the plasticity of mesothelial cells has also been implicated in these serosal pathologies. Although a mesothelial stem cell has not yet been identified, growing evidence based on their primitive embryological origin and reported ability to differentiate into fibroblast or myofibroblast-like cells, strongly supports the concept that a population of mesothelial progenitor cells exist. This thesis tested the hypothesis that mesothelial-derived cells are multipotent adult stem-like cells. More specifically, 1) malignant mesothelioma tumours contain bone tissue that is derived from the differentiation of MM cells into osteoblast-like cells, 2) mesothelial cells are multipotent and can differentiate into cells of other mesenchymal lineages including osteoblasts and adipocytes in a manner similar to mesenchymal stem cells and 3) mesothelial progenitor cells derive from the bone marrow and incorporate into regenerating mesothelium. In vivo bone formation was assessed in human and murine MM tumours and areas of osteoid and bone tissue were identified using histological methods.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2008|