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Stem Cells

Duncan J. Stewart


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Conference: 2010 International PHA Conference and Scientific Sessions

Release Date: 06.22.2010

Presentation Type: Scientific Sessions

Watch Now! http://www.phamultimedia.org/Conference2010_Scientific_Sessions/2010Jun25_FRI27_Stem-Cells/Player.html

This presentation will review the preclinical studies assessing cell-based therapies for PAH. In PAH, there is increasing evidence that endothelial cell (EC) apoptosis is the initiating lesion, and this then leads to a series of consequences that can directly or indirectly result in degeneration or obliteration of precapillary arterioles. Therefore, administration of bone marrow-derived endothelial progenitor cells (EPCs), that are known to play an important role in the repair and regeneration of systemic vessels, could be effective in preventing and even reversing PAH in experimental models. Results from studies mainly using the monocrotaline (MCT) model of PAH confirmed the near complete prevention of the development of pulmonary hypertension when these cells are delivered 3 days after MCT. Moreover, delaying cell therapy until 3 weeks post injury, at which time pulmonary hypertension is fully apparent, also prevented further progression; whereas, delivery of EPCs that were genetically engineered to overexpress endothelial NO-synthase (eNOS) reversed established PAH. In addition to being an important endothelial vasodilating factor, NO plays a key role in regulating vascular growth and remodeling, and is a critical factor in angiogenesis. Based on these preclinical findings, we have initiated an early phase clinical trial to test the efficacy and possible safety of eNOS-transfected autologous EPCs in patients with refractory PAH, and the design and preliminary results of this study will be discussed.