Less is More: Oxygen and Stem Cell Regeneration

Citation

Csete, Marie Elizabeth (2000) Less is More: Oxygen and Stem Cell Regeneration. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/MP6F-KN97. https://resolver.caltech.edu/CaltechETD:etd-12032003-091634

Abstract

Recent years have witnessed an explosion in the identification and understanding of stem cells, affording new cellular reagents for the study of regeneration in vitro. Traditionally, regeneration is studied in tissue culture in which the gaseous environment surrounding the cells contains about 20% oxygen. Cells in our bodies are never exposed to such high levels of oxygen, well out of normal physiologic range. In this work, stem cell regeneration in several systems was studied in traditional 20% oxygen culture and in oxygen levels more reflective of normal physiology. These lower oxygen-cultured progenitors behaved differently than those cultured in traditional environments. In several stem cell systems low oxygen significantly increased proliferation of progenitor populations, and in central nervous system stem cells, also decreased apoptotic death. More physiologic levels of oxygen in culture also led to regeneration of different daughter progeny populations with a distribution of phenotypes distinct from that generated in 20% oxygen. For example in CNS stem cells, a significantly greater yield of dopaminergic and serotonergic neurons was generated in low oxygen compared to 20% oxygen. Skeletal muscle satellite stem cells in high oxygen were significantly more likely to assume an adipocyte phenotype than those cultured in low oxygen. Furthermore, genes expressed during regeneration in physiologic vs. 20% oxygen were different from each other in timing and in abundance. These data suggest that oxygen manipulations will be useful to increase the survival and expansion of progenitor populations for research and possible transplantation, as well as for the survival and expansion of selected regenerated progeny. Furthermore, oxygen levels are a useful manipulation to help isolate and identify pathways used during regeneration and differentiation.

Thesis Files