Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Reinisch, A.
Towards a better understanding of non-hematopoietic stem and progenitor cell biology and function
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medical University of Graz; 2010. pp.121.
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- Autor*innen der Med Uni Graz:
- Reinisch Andreas
- Betreuer*innen:
- Dohr Gottfried
- Linkesch Werner
- Strunk Dirk
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- Abstract:
- The basic concept of regenerative medicine is a curative treatement of diseases through transplantation of cells that bear the potential to regenerate damaged tissue by direct cell replacement or by supportive functions. Nevertheless this straightforward idea of simply transplanting stem and progenitor cells to cure patients partly struggles because basic prerequistes needed to reach this ambiguous goal have so far not been able to be fulfilled. These prerequists include the efficient production of stem cell transplants in sufficient quality and quantity, availability of preclinical models to test transplant functionality and appropriate methodologies to evaluate cell fate early after application that subsequently can help to modulate and improve transplantation protocols. This study mostly deals with production of cellular transplants in appropriate quantity and functionality. The scarcity of stem and progenitor cell populations that are primarily used for the purpose of regenerative medicine is the reason that these cells have to be expanded in vitro before use. We developed GMP-compliant protocols for isolation and propagation of non-hematopoietic progenitor cells including endothelial colony-forming progenitor cells and multipotent mesenchymal stromal cells. Human umbilical cord blood has been employed as an alternative source to produce virtually pure cell transplants for putative clinical applications. Xenogenic fetal bovine serum was replaced by highly efficient human pooled platelet lysate as a new source for growth factors and reduces risk of animal pathogen transmission, xeno-immunisation therefore facilitating clinical applicability. Progenitor cells, cultured under fully humanized conditions, were highly functional in vitro and were capable of forming human tissue including perfused vessels and mature bone when transplanted into immune deficient mice in vivo. To track these cells in vivo, superparamagnetic iron oxid nanoparticles were used for cellular labeling and magnetic resonance imaging strategies were optimized to allow for high resolution single cell imaging. Results obtained should help to develop new procedures of stem and progenitor cell transplantation for organ regeneration