The identification of a multi-potent stem cell-like population (SP) within the adult murine heart infers new methods of cardiac repair, i.e. stem cells compensate for damage by generating new cardiomyocytes. Several studies have emphasized the dominance of the tissue microenvironment on the differentiation & functional properties of stem cells. Of particular interest was Cardiotrophin-1 (CT-1), a member of the Interleukin-6 (IL-6) family of cytokines. To assess whether CT-1 functioned as an activator of cardiac SP cells in the murine heart, an adenovirus containing the full length CT-1 driven by a ubiquitous promoter was generated. The adenovirus was administered via intra-cardiac injections and the effects of CT-1 were primarily assessed using fluorescence-activated cell sorting (FACS) analysis. Analysis showed a temporary increase in the cardiac SP of CT-1 injected hearts. A closer look at the SP cells in other tissues (liver, skeletal muscle and bone marrow) demonstrated that this phenomenon was cardiac specific. Interestingly the cardiac SP expressed the Leukemia Inhibitory Factor (LIF) receptor, which is required for CT-1 signaling through the 130 pathway. Protein analysis also showed that STAT3, a downstream member of the 130 pathway becomes activated in the heart during CT-1 injections. Preliminary results from co-culture experiments suggested that this increase was also accompanied by SP cell differentiation. These results proposed that CT-1 not only increased the cardiac SP size but may have also activated a cardiac differentiation program. The existence of a potential biologic stimulant (CT-1) for cardiac stem cells is an exciting prospect and offers support to the notion that cardiac repair may become a viable therapeutic option in the not too distant future.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/26946 |
| Date | January 2005 |
| Creators | Knudson, Jennifer Caroline |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 118 p. |
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