Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies

Martin‐Rendon, Enca

doi:10.1161/circresaha.115.307540

Cited by 20 publications

(6 citation statements)

References 37 publications

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“…This was the theme of 2 very recent reviews published by well-known experts in the field[55,56]. As one would expect, the first variation factor to point the finger to is related to differences in the methodology used in conducting systematic reviews.…”

Section: Meta-analysismentioning

confidence: 99%

“…Although ACCRUE (Meta-Analysis of Cell-Based Cardiac Studies; NCT01098591) database comprised a pool of 1252 IPDs from 12 randomized studies in AMI settings, it included only about 60% of the available published trials, as a result raising concern for potential bias. Of course, there are some other disparity factors involved, such as insufficient power of included studies, patients’ heterogeneity and statistical heterogeneity[55,56]. …”

Section: Meta-analysismentioning

confidence: 99%

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Fifteen years of bone marrow mononuclear cell therapy in acute myocardial infarction

Micheu

Dorobanțu

2017

WJSC

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In spite of modern treatment, acute myocardial infarction (AMI) still carries significant morbidity and mortality worldwide. Even though standard of care therapy improves symptoms and also long-term prognosis of patients with AMI, it does not solve the critical issue, specifically the permanent damage of cardiomyocytes. As a result, a complex process occurs, namely cardiac remodeling, which leads to alterations in cardiac size, shape and function. This is what has driven the quest for unconventional therapeutic strategies aiming to regenerate the injured cardiac and vascular tissue. One of the latest breakthroughs in this regard is stem cell (SC) therapy. Based on favorable data obtained in experimental studies, therapeutic effectiveness of this innovative therapy has been investigated in clinical settings. Of various cell types used in the clinic, autologous bone marrow derived SCs were the first used to treat an AMI patient, 15 years ago. Since then, we have witnessed an increasing body of data as regards this cutting-edge therapy. Although feasibility and safety of SC transplant have been clearly proved, it’s efficacy is still under dispute. Conducted studies and meta-analysis reported conflicting results, but there is hope for conclusive answer to be provided by the largest ongoing trial designed to demonstrate whether this treatment saves lives. In the meantime, strategies to enhance the SCs regenerative potential have been applied and/or suggested, position papers and recommendations have been published. But what have we learned so far and how can we properly use the knowledge gained? This review will analytically discuss each of the above topics, summarizing the current state of knowledge in the field.

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Section: Meta-analysismentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

Fifteen years of bone marrow mononuclear cell therapy in acute myocardial infarction

Micheu

Dorobanțu

2017

WJSC

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“…Cell therapy of coronary artery disease has evolved rapidly from bench to bedside; however, despite positive results in murine models of MI, small‐ or medium‐sized clinical studies and meta‐analyses have only shown modest benefit in humans 4, 5, 6, 7. This could be principally because of the use of inappropriate and ill‐defined cell populations, which calls for a continued search for optimal, quality‐assured cell products.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

Alvino

Fernández‐Jiménez

Rodriguez‐Arabaolaza

et al. 2018

JAHA

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BackgroundTransplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model.Methods and ResultsWe performed a blind, randomized, placebo‐controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following in vitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone.ConclusionsImmunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.

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“…Clinical studies with skeletal myoblasts, bone marrow-derived cells, mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) have shown feasibility and initial evidence of efficacy ( Assmus et al, 2002 , de Jong et al, 2014 , Hare et al, 2009 , Menasche et al, 2008 , Sant'anna et al, 2010 ). After multiple systematic reviews and meta-analyses, the consensus is that transplantation of adult bone marrow cells modestly improves ventricular function, infarct size, and remodeling in patients with CHD compared with standard therapy, and these benefits persist during long-term follow-up ( Martin-Rendon, 2016 ). Bone marrow cell transplantation also reduces the incidence of death, recurrent MI, and stent thrombosis in patients with CHD ( Jeevanantham et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

Ellison

Madeddu

2017

Pharmacology & Therapeutics

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Ischaemic diseases remain a major cause of morbidity and mortality despite continuous advancements in medical and interventional treatments. Moreover, available drugs reduce symptoms associated with tissue ischaemia, without providing a definitive repair. Cardiovascular regenerative medicine is an expanding field of research that aims to improve the treatment of ischaemic disorders through restorative methods, such as gene therapy, stem cell therapy, and tissue engineering. Stem cell transplantation has salutary effects through direct and indirect actions, the latter being attributable to growth factors and cytokines released by stem cells and influencing the endogenous mechanisms of repair. Autologous stem cell therapies offer less scope for intellectual property coverage and have limited scalability. On the other hand, off-the-shelf cell products and derivatives from the stem cell secretome have a greater potential for large-scale distribution, thus enticing commercial investors and reciprocally producing more significant medical and social benefits. This review focuses on the paracrine properties of cardiac stem cells and pericytes, two stem cell populations that are increasingly attracting the attention of regenerative medicine operators. It is likely that new cardiovascular drugs are introduced in the next future by applying different approaches based on the refinement of the stem cell secretome.

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Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies

Cited by 20 publications

References 37 publications

Fifteen years of bone marrow mononuclear cell therapy in acute myocardial infarction

Fifteen years of bone marrow mononuclear cell therapy in acute myocardial infarction

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction

Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

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