ArticleAmerican journal of physiology. Heart and circulatory physiology2010
Phosphodiesterase inhibition with tadalafil provides longer and sustained protection of stem cells.
Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 59 citations in OpenAlex.
- Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.Cells · 2024Review
- Priming mesenchymal stem cells to develop "super stem cells".World journal of stem cells · 2024Article
- Review
- Tadalafil Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells-Derived Exosomes in Pulmonary Hypertension by Upregulating miR-29a-3p.International journal of nanomedicine · 2024Article
- Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects.Stem cell research & therapy · 2022Review
- Pharmacological preconditioning with phosphodiestrase inhibitor: an answer to stem cell survival against ischemic injury through JAK/STAT signaling.Heart failure reviews · 2020Review
- Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy.Stem cell research & therapy · 2020Review
- Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair:Cellular and molecular bioengineering · 2018Article
- Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue.Acta biomaterialia · 2018Article
- Tadalafil, a long acting phosphodiesterase inhibitor, promotes bone marrow stem cell survival and their homing into ischemic myocardium for cardiac repair.Physiological reports · 2017Article
- Role of Nitric Oxide, Nitric Oxide Synthase, Soluble Guanylyl Cyclase, and cGMP-Dependent Protein Kinase I in Mouse Stem Cell Cardiac Development.Stem cells international · 2016Article
- Mesenchymal Stem Cells in Cardiology.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Tadalafil therapy and severe chronic foot wound resolution.International wound journal · 2015Article
- Tadalafil, a Phosphodiesterase Inhibitor Protects Stem Cells over Longer Period Against Hypoxia/Reoxygenation Injury Through STAT3/PKG-I Signaling.Stem cells and development · 2015Article
- Optimization of the cardiovascular therapeutic properties of mesenchymal stromal/stem cells-taking the next step.Stem cell reviews and reports · 2013Review
- Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.PloS one · 2013Article
- Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We hypothesized that inhibition of the cGMP-specific enzyme phosphodiesterase 5A (PDE5A) promoted cGMP/protein kinase G (PKG) activity to condition stem cells for enhanced survival and proliferation. One-time tadalafil treatment (1 μM for 30 min) of mesenchymal stem cells ((Tada)MSCs) provided sustained protection of cells for 36 h. Higher cGMP activity with concomitantly increased PKG1 activity was observed in (Tada)MSCs, which peaked within 12 h after tadalafil treatment. Pretreatment with PKG1 blockers (1 μM KT-5823 or 20 nM K-252a) or transduction with adenoviral PKG1-short-hairpin RNA abolished tadalafil-induced cytoprotection of the cells. A higher proliferation rate was observed in (Tada)MSCs compared with nontreated MSCs ((Cont)MSCs). In a rat model of acute myocardial infarction, (Tada)MSCs transplanted 0 and 24 h after tadalafil treatment showed higher survival compared with (Cont)MSCs on day 2 and day 4 after engraftment. (Tada)MSCs transplanted 48 h after tadalafil treatment lost their protection on both day 2 and day 4 after engraftment, and their rate of survival was similar to (Cont)MSCs. Reduced terminal dUTP nick end-labeling positivity (P < 0.01 vs. (Cont)MSCs) and higher proliferation of (Tada)MSCs (P < 0.01 vs. (Cont)MSCs) was observed in the infarcted heart. Fluorescence immunostaining revealed neomyogenesis in both the infarct and peri-infarct areas. Blood vessel density was significantly increased in group 2 compared with group 1. Transthoracic echocardiographic heart function revealed significant preservation of the indexes of left ventricle contractility and attenuation of remodeling in (Tada)MSC-engrafted animal hearts (group 2) compared with (Cont)MSCs (group 1). PDE5A inhibition using long-acting tadalafil is an innovative approach to promote stem cell survival and proliferation in the infarcted heart.
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