Joep Egbert Coenraad Eding

Similar effect of autologous and allogeneic cell therapy for ischemic heart disease : Systematic review and meta-analysis of large animal studies

Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P <0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P =0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials. # Novelty and Significance {#article-title-48}Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P=0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials.

A systematic review of computed tomography detection of cartilage invasion in laryngeal carcinoma.

This systematic review aimed to assess the diagnostic value of computed tomography (CT) in detecting cartilage invasion among patients with laryngeal carcinoma.

The Efficacy of Cardiac Anti-miR-208a Therapy Is Stress Dependent

MicroRNAs (miRNAs) are important regulators of biology and disease. Recent animal efficacy studies validate the therapeutic benefit of miRNA modulation and underscore the therapeutic value of miRNA-targeting oligonucleotides. However, whether disease conditions (stress) influence the pharmacological effects of an anti-miR is currently unknown. To study the effect of disease on target regulation after anti-miR treatment, we injected animals with anti-miR-208a, a synthetic oligonucleotide that inhibits the cardiomyocyte-specific miR-208a. Our data indicate that the presence of stress increases the number of regulated miR-208a targets, and that higher stress levels correlate with stronger target derepression. Additionally, the type of stress also influences which targets are regulated upon miR-208a inhibition. Studies in a large animal model indicate a similar stress-dependent anti-miR effect. Subsequent in vitro studies suggest that the influence of stress on anti-miR efficacy depends at least in part on increased cellular anti-miR uptake. These data indicate that the pharmacological effect of anti-miRs is stronger under disease conditions, and that both the type and severity of disease determine the therapeutic outcome. These facts will be important for assessing the therapeutic dose and predicting the therapeutic outcome when applying anti-miRs in a clinical setting.

Publisher Correction: Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies

Large animal models are essential for the development of novel therapeutics for myocardial infarction. To optimize translation, we need to assess the effect of experimental design on disease outcome and model experimental design to resemble the clinical course of MI. The aim of this study is therefore to systematically investigate how experimental decisions affect outcome measurements in large animal MI models. We used control animal-data from two independent meta-analyses of large animal MI models. All variables of interest were pre-defined. We performed univariable and multivariable meta-regression to analyze whether these variables influenced infarct size and ejection fraction. Our analyses incorporated 246 relevant studies. Multivariable meta-regression revealed that infarct size and cardiac function were influenced independently by choice of species, sex, co-medication, occlusion type, occluded vessel, quantification method, ischemia duration and follow-up duration. We provide strong systematic evidence that commonly used endpoints significantly depend on study design and biological variation. This makes direct comparison of different study-results difficult and calls for standardized models. Researchers should take this into account when designing large animal studies to most closely mimic the clinical course of MI and enable translational success.

Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart DiseaseNovelty and Significance: Systematic Review and Meta-Analysis of Large Animal Studies

Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P <0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P =0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials. # Novelty and Significance {#article-title-48}Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P=0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials.

Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart DiseaseNovelty and Significance

Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P <0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P =0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials. # Novelty and Significance {#article-title-48}Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5; P<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331; P=0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials.