Hypoxic Preconditioning of Stem Cells to Treat Myocardial Infarction

2013 ◽  
pp. 199-210
Author(s):  
Simi Chacko ◽  
Periannan Kuppusamy
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Hypoxic Preconditioning

scholarly journals HYPOXIC PRECONDITIONING OF STEM CELLS AS A NEW APPROACH TO INCREASE THE EFFICACY OF CELL THERAPY FOR MYOCARDIAL INFARCTION

2013 ◽  
Vol 68 (12) ◽  
pp. 16-25 ◽  
Author(s):  
L. N. Maslov ◽  
Yu. K. Podoksenov ◽  
A. G. Portnichenko ◽  
A. V. Naumova
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Cell Therapy ◽  
Survival Rates ◽  
Hypoxic Preconditioning ◽  
Erythropoietin Receptor ◽  
Receptor Expression ◽  
Ischemic Region

During the last decade, stem cell research has developed at an accelerated pace. Various types of stem cells have been tested for myocardial infarction therapy. Despite the preclinical benefits of cell therapy success in clinical trials remains modest. The main obstacles to regeneration of the infarcted heart using stem cells are: 1) not every stem cell type can differentiate into cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been shown to improve transplantation efficacy of mesenchymal stem cells and cardiac progenitor cells in animal models of myocardial infarction. It has also been shown that transplantation of preconditioned cells decreases infarct size, prevents postinfarction remodeling of the heart, and positively modulates development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents extensive death of transplanted cells due to necrosis and apoptosis during long-term hypoxia or oxidative stress. The protective effect of HP is based on three main processes: (1) modification of cell phenotypes to help survival during hypoxia (enhancement of HIF-1α expression, ERK1/2 and Akt activation, enhancement of erythropoietin receptor expression and erythropoietin production, and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2) upregulation of various secretable factors including the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2 and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors, which play an important role in mobilization and homing of stem cells in the ischemic region. .

Strategies for Recruitment of Stem Cells to Treat Myocardial Infarction

2015 ◽  
Vol 21 (12) ◽  
pp. 1584-1597 ◽  
Author(s):  
Muhammad Shafiq ◽  
Sang-Hoon Lee ◽  
Youngmee Jung ◽  
Soo Kim
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells

Effect of SDF-1 α on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction

2014 ◽  
Vol 20 (12) ◽  
pp. 1964-1970 ◽  
Author(s):  
Alexander Schuh ◽  
Simone Konschalla ◽  
Andreas Kroh ◽  
Andreas Schober ◽  
Nikolaus Marx ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells

Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction

2014 ◽  
Vol 20 (12) ◽  
pp. 2023-2029 ◽  
Author(s):  
Jian Chen ◽  
Shaoxin Zheng ◽  
Hui Huang ◽  
Suihua Huang ◽  
Changqing Zhou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Rat Model ◽  
Nerve Growth ◽  
Cardiac Nerve ◽  
Nerve Sprouting

Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Von Lewinski ◽  
B Merkely ◽  
I Buysschaert ◽  
R.A Schatz ◽  
G.G Nagy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Early Recovery ◽  
Ventricular Ejection Fraction ◽  
Combined Application

Abstract Background Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model. Purpose We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction. Methods The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF <45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect >3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos. Results Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1). Conclusions Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor

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