Stem cell therapy is emerging as a possible method for treating many diseases and disorders, such as cardiovascular disease. In particular, stem cells may be able to revive the dead tissue caused by acute myocardial infarction (heart attack). Adipose-derived stem cells were labelled with 18F-fluorodeoxyglucose (FDG) and superparamagnetic iron oxide (SPIO) particles, for imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), respectively, and injected into several rats following induced myocardial infarction. Stem cell retention in the heart was investigated following three injection sites; two within the heart (intramyocardial and left intraventricular), and one easily accessible vein (tail vein). The PET and MR images were registered and the initial distributions analyzed using region of interest (ROI) analysis, to determine which injection method would result in the highest stem cell retention in the infarcted heart. The ROI results determined that the intramyocardial injection had the highest % injected dose (%ID) in the heart with 14 +/- 4%, followed by left intraventricular and tail vein with %IDs of 3.6 +/- 0.8% and 1.2 +/- 0.6%, respectively. The results indicate that stem cell delivery via intramyocardial injection should be utilized for optimal retention in the heart.

Both cDNA tag-based and DNA chip hybridization assays have revealed widespread transcriptional activity across mammalian genomes, providing a rich source of novel protein-coding and non-coding transcripts. Annotation and functional evaluation of this undefined transcriptome space represents a major step towards the comprehensive definition of biomolecules regulating the properties of living cells, including embryonic stem cells (ESCs) and their derivatives. In this study I analysed 87 rare mRNA transcripts from human ESCs that mapped uniquely to the human genome, in regions lacking evidence for known genes or transcripts. In addition, the transcripts appeared enriched in the hESC transcriptome as enumerated by serial analysis of gene expression (SAGE). Full-length transcripts corresponding to twelve novel LongSAGE tags were recovered and evaluated with respect to gene structure, protein-coding potential, and gene regulatory features. In addition, transcript abundance was compared between RNA isolated from undifferentiated hESCs and differentiated cells. Analysis of full-length transcripts revealed that the novel ORFs did not exceed a size of 129 amino acids and no matches were observed to well characterized protein domains. Interesting protein level predictions included small disulfide-bonded proteins, known members of which are important in a variety of biological processes. Transcripts evaluated for differential expression by real-time RT-qPCR (Reverse Transcription followed by real-time quantitative Polymerase Chain Reaction) were found to be variably expressed (0.2- to 4.5-fold) in Day-2 or Day-4 retinoic acid-induced differentiation cultures compared to undifferentiated hESCs. Relative quantitation using a universal reference RNA (derived from pooled adult tissues) showed large differences in novel transcript levels (0.002- to 35-fold) compared to hESCs. Collectively, these results provide a detailed analysis of a set of novel hESC transcripts and their abundance in early and adult differentiated cell types, both of which may advance our understanding of the transcriptional events governing stem cell behavior.

Myocardial infarction is the most common cause of heart failure and remains one of the leading causes of morbidity and mortality in humans. Stem cells are important in the maintenance and repair of adult tissues. Hoechst effluxing cells, termed side population cells are a rare subset of cells found in adult tissues that are highly enriched for stem and progenitor cell activity. Recent studies have suggested that Sca-1+/CD31- cardiac side population cells are capable of differentiation into cardiomyocytes in vitro. However, the response of cardiac side population cells to myocardial injury remains unknown in vivo. In this study, we directly transplanted Sca-1+/CD31- cardiac side population cells into an acutely infarcted mouse heart. After two weeks, the transplanted cells were found to express cardiomyocyte or endothelial cell markers. Importantly, when these cells were transplanted into a remote nonischemic part of the heart after MI, they were able to migrate to the damaged myocardium. Consistent with these cells homing property, we found that SDF-1α, a chemotactic chemokine and its receptor, CXCR4 were up-regulated in the damaged myocardium and on Sca-1+/CD31- cardiac SP cells respectively following an acute myocardial infarction. We further showed that SDF-1α was able to induce migration of Sca-1+/CD31- cardiac side population cells in vitro. Our results have therefore suggested that Sca-1+/CD31- cardiac side population cells are able to migrate to damaged myocardium from non-ischemic myocardium and differentiate into cardiomyocytes as well as endothelial cells in the acutely infarcted mouse heart. We postulate that the SDF-1α/CXCR4 interaction may play an important role in the migration of these cells. Understanding and enhancing these processes may hold enormous potential possibilities for therapeutic myocardial regeneration for the treatment of cardiovascular disease.

Thesis (Ph.D)--University of Tulsa, 1989. / Bibliography: leaves 226-232.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 97-124) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 85-93) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Robert Butera; Committee Member: Pamela Bhatti; Committee Member: Todd McDevitt

Thesis (M. S.)--Computer Science, Georgia Institute of Technology, 2009. / Committee Chair: Dr. Samuel Dudley; Committee Member: Dr. Micheal Davis; Committee Member: Dr. Robert Butera