Medizinische Universität Graz - Research portal
Selected Publication:
Kittinger, C.
AC 133+ Umbilical Cord Blood Stem Cells as a Tool for Myocardial Improvement in the Ischemic Rat Heart
[ Dissertation ] Medical University of Graz; 2004. pp.
- Authors Med Uni Graz:
- Kittinger Clemens
- Advisor:
- Dohr Gottfried
- Preisegger Karl Heinz
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- Abstract:
- In recent years, umbilical cord blood (UCB) emerged as a feasible alternative source of hematopoietic progenitors for stem cell transplantation and as graft for the treatment of carious acquired and genetic diseases. However, the stem cell content of UCB is often not sufficient neither for the use as a graft for adult patients nor for multiple applications such as regeneration after myocardial infarction. Thus, a reproducible method of generation of large numbers of HSC from limited numbers of input is needed for UCB to combat graft failure in adult recipients and to become a safe and reliable resource for adult HSC transplantation as well as a useful source for various and repeatable stem cell therapies including, e.g., the repair of myocardial infarction. The major aim of this thesis was to prove expanded hematopoietic stem cells (AC133+) capable of improving myocardial infarction in a rodent model. For this purpose, we transplanted not expanded and expanded cells into nude rats and investigated their ability to migrate to the infracted area and their capability of improving myocardial function: we examined the in vivo properties of these expanded SC in a rat model of acute and chronic cardiac infarction. AC133+ selected progenitor cells were expanded with a four cytokine cocktail (TPO, SCF, flt-3, IL-6) CM-Dil labelled and injected intravenously into athymic nude rats. We were able to identify fluorescently labeled AC133+ cells in the infracted areas, indicating that the migratory capacity of expanded AC133+ cells was similar to unmanipulated progenitor cells. Further, left ventricular ejection fraction (LVEF) was improved significantly in both groups. However, immunohistochemical experiments on cryo-section of the extracted hearts did not allow detection of injected haematopoietic stem cells that had acquired endothelial or myocardial cell-features. Our results demonstrate that AC133+ stem cells can be expanded reproducibly and thus might provide a valuable source for regenerating ischemic myocardium in clinical settings, since the properties in terms of i mproving heart function are not altered by expansion.