in-vivo non-viral delivery of shrna for mi, page-6

Another nice study that should be of interest to stem cell companies. Hello!!! Mesoblast,... where are you???

Preconditioning by Phosphodiesterase-5 Inhibition Improves Therapeutic Efficacy of Adipose Derived Stem Cells Following Myocardial Infarction in Mice.

Stem Cells. 2011 Nov 18;

Abstract

RATIONALE: Enhancing the therapeutic potential of stem cells in ischemic microenvironments by novel preconditioning strategies is critical for improving cellular therapy. OBJECTIVE: We tested the hypothesis that inhibition of phosphodiesterase-5 (PDE-5) with sildenafil (Viagra) or knockdown with a silencing vector in adipose derived stem cells (ASCs) would improve their survival and enhance cardiac function following myocardial implantation in vivo. METHODS AND RESULTS: ASCs were treated with sildenafil or PDE-5 silencing vector shRNA (shRNA(PDE-5) ) and subjected to simulated ischemia/re-oxygenation in vitro. Both sildenafil and shRNA(PDE-5) significantly improved viability, decreased necrosis, apoptosis, and enhanced the release of growth factors, VEGF, b-FGF, and IGF. Inhibition of protein kinase G (PKG) reversed these effects. To show the beneficial effect of preconditioned ASCs in vivo, adult male CD-1 mice underwent myocardial infarction. Preconditioned ASCs (4×10(5) ) were directly injected intramyocardially. Preconditioned ASCs-treated hearts showed consistently superior cardiac function as compared with non-preconditioned ASCs after 4 weeks of treatment. This was associated with significantly reduced fibrosis, increased vascular density and decreased resident myocyte apoptosis as compared to mice receiving non-preconditioned ASCs. VEGF, b-FGF, and Ang-1 were also significantly elevated 4 weeks after cell therapy with preconditioned ASCs treatment. CONCLUSIONS: We conclude that preconditioning by inhibition of PDE-5 can be a powerful novel approach to improve stem cell therapy following myocardial infarction.

PMID: 22102597 [PubMed - as supplied by publisher]

http://medicine.journalfeeds.com/hematology/stem-cells/preconditioning-by-phosphodiesterase-5-inhibition-improves-therapeutic-efficacy-of-adipose-derived-stem-cells-following-myocardial-infarction-in-mice/20111130/