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Treatment of Pulmonary Arterial Hypertension with Circulating Angiogenic Cells.
MedLine Citation:
PMID:  21398496     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (CACs, also termed early endothelial progenitor cells) due to their ability to home to sites of vascular injury and regenerate blood vessels. We studied the efficacy of human CAC therapy in the treatment of pulmonary arterial hypertension at two different stages of disease severity. Cells were isolated from peripheral blood and administered to nude rats on day 14 ("early") or day 21 ("late") post monocrotaline injection. Control group received monocrotaline but no cell treatment. Disease progression was assessed using right heart catheterization and echocardiography at multiple timepoints. Survival differences, right ventricular hypertrophy (RVH) and vascular hypertrophy were analyzed at study endpoint. Quantitative PCR was performed to evaluate cell engraftment. Treatment with human CACs either at the early or late timepoints did not result in increased survival and therapy did not prevent or reduce the severity of disease compared to control. Histological analysis of RVH and vascular muscularization showed no benefit with therapy compared to control. No detectable signal was seen of human transcript in transplanted lungs at 14 or 21 days post-cell transplant. In conclusion, CAC therapy was not associated with increased survival and did not result in either clinical or histologic benefits. Future studies should be geared towards either earlier therapeutic timepoints with varying doses of unmodified CACs or genetically modified cells as a means of delivery of factors to the pulmonary arterial circulation.
Authors:
Rachel Mirsky; Sarah Jahn; Juha W Koskenvuo; Richard E Sievers; Sarah M Yim; Carissa Ritner; Harold S Bernstein; Franca S Angeli; Andrew J Boyle; Teresa De Marco; Yerem Yeghiazarians
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-11
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  -     ISSN:  1522-1504     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University of California, San Francisco.
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