Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kulterer, B.
Gene Expression Analysis of Human Bone Marrow derived Mesenchymal Stem Cells during ther Proliferation and Differentiation
[ Dissertation ] Medical University of Graz; 2005. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Preisegger Karl Heinz
- Altmetrics:
- Abstract:
- Stem-cell based therapies of human diseases are rapidly expanding. Processing and engineering of single selected cells for the therapy of a wide range of disease are increasingly possible. Mesenchymal stem cells derived form bone marrow are a very promising cell population for human treatment and have already been proven experimentally to improve cardiac function after infarction, or symptoms of bone and cartilage defects, Alzheimers and Atherosclerosis. In recent clinical trails the safety of adult stem cells has been demonstrated but because of their rarity in the mononuclear cell fraction high grade expansion and modification of these cells is necessary prior to clinical use. However, considerable concerns are arising when using ex vivo manipulated stem cells. To address the safety issue for clinical applications the gene expression profile of expanded MSC was investigated to clarify, if the cells are developing in a specific committed differentiation line or in another aberrant way during in vitro long-term cultivation. Specifically, hMSC were monitored during their proliferation ex vivo with respect to surface marker profile, differentiation potential and expression profiling using high-density oligonucleotide microarrays. The found results strengthen the risk free use ex vivo expanded hMSC for different therapapeutical applications. Further, after demonstrating that hMSC can be expanded in vitro without obvious signs of aberrant development, they seem to be an ideal source of cells to generate osteoblasts for treating common bone disease. Hence, in the second part of the work transcriptional profiling of hMSC during their differentiation into osteoblasts was performed. With the hereby obtained results it was possible to reconstruct, for the first time in a human model, the three main phases of osteogenic development. In addition, by mapping the expression profiles on pathways, a non-parallel regulation of the TGF-Beta pathway and Smad pathway during osteogenic differentiated could be illustrated. Last but not least, the genetic profile of in vitro differentiated osteoblasts was compared with the genetic profile in vivo developed normal osteoblasts. The results showed that the in vitro and in vivo development of osteoblasts seemed to proceed more or less in parallel with only some mentionable discrepancies.