Juan Carlos Chachques

• MD, PhD
• Managing Director at Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the...

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to low cell retention, cell death in inflammatory and poor angiogenic infarcted areas, secondary migration. Cells interact with their microenvironment through integrin mechanoreceptors that control their survival/apoptosis/differ...

This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton’s jelly (WJ) was carried out using “explant” and mononuclear cells by the density gradient from umbilical blood and characterized by flow cytometry. hMSCs were...

Cardiac cells interact with the extracellular matrix (ECM) proteins through integrin mechanoreceptors that control many cellular events such as cell survival, apoptosis, differentiation, migration, and proliferation. Integrins play a crucial role in cardiac development as well as in cardiac fibrosis and hypertrophy. Integrins recognize oligopeptide...

A challenge in contractile restoration of myocardial scars is one of the principal aims in cardiovascular surgery. Recently, a new potent biological tool used within healing processes is represented by exosomes derived from mesenchymal stem cells (MSCs). These cells are the well-known extracellular nanovesicles released from cells to facilitate cel...

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (8): 3350-3364–DOI: 10.26355/eurrev_202104_25747–PMID: 33928623, published online 30 April, 2021. After publication, the authors requested to correct the Acknowledgements of the above-mentioned article. There are amendments to this paper. The Publisher apologizes for...

Objective: The purpose of this article was to review our clinical experience with COVID-19 patients observed in the Cardiovascular Division of Pompidou Hospital (University of Paris, France) and the Department of Neurology of the Eastern Piedmont University (Novara, Italy), related to the impact on the cardiovascular, hematological, and neurologic...

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease originated in Wuhan, China, in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severe form of the disease is often associated with acute respiratory distress syndrome (ARDS), and most critically ill patients require mechanical ventilation...

Ross operation might be a valid option for congenital and acquired left ventricular outflow tract disease in selected cases. As the pulmonary autograft is a living substitute for the aortic root that bioinspired the Ross operation, we have created an experimental animal model in which the vital capacity of the pulmonary autograft (PA) has been stud...

Three dimensional (3D) printing, which consists in the conversion of digital images into a 3D physical model, is a promising and versatile field that, over the last decade, has experienced a rapid development in medicine. Cardiovascular medicine, in particular, is one of the fastest growing area for medical 3D printing. In this review, we firstly d...

Objectives: Prevention of postischaemic ventricular dilatation progressing towards pathological remodelling is necessary to decrease ventricular wall deterioration. Myocardial tissue engineering may play a therapeutic role due to its capacity to replace the extracellular matrix, thereby creating niches for cell homing. In this experimental animal...

Sudden cardiac arrest (SCA) remains a major problem for health authorities worldwide. Insufficiencies of current cardiopulmonary resuscitation (CPR) are most probably related to an inappropriate concept and applied methods that still concentrate on heartbeat as priority, instead of blood circulation to maintain organs' perfusions. The aim of this w...

The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously deve...

Objectives: Use of resorbable external reinforcement of the pulmonary autograft during the Ross operation has been suggested, but the differential regional potential for dilation of the aorta, mainly regarding the neo-root and the neo-Valsalva sinuses, represents an unresolved issue. Auxetic materials could be useful in preventing dilation given t...

Post-ischemic ventricular dilatation and cardiac remod-eling refers to the changes in size, shape, structure and physiology of the heart after injury to the myocardium. Dilated cardiomyopathy from many causes results in a change in ventricular geometry, whereby the elliptical chamber becomes more spherical. This change in architecture alters myocar...

Abstract BACKGROUND: Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular researc...

Ischemia produced as a result of myocardial infarction might cause moderate or severe tissue death. Studies under development propose grafting stem cells into the affected area and we hypothesize that this mechanism could be enhanced by the application of a “bioactive implant.” The implant herein proposed consists of a thin porous elastomeric membr...

Objectives: To circumvent the issue of pulmonary autograft (PA) dilation after the Ross procedure, surgical reinforcement strategies have been suggested in clinical or anecdotal series. However, no preclinical large-animal model of the Ross procedure is available, which is needed to enable full comprehension of the pathologic mechanisms and the ef...

Contractile restoration of myocardial scars remains a challenge with important clinical implications. Here, a combination of porous elastomeric membrane, peptide hydrogel, and subcutaneous adipose tissue-derived progenitor cells (subATDPCs) was designed and evaluated as a bioimplant for cardiac regeneration in a mouse model of myocardial infarction...

Objective: To assemble a biohybrid cardiac patch consisting of a large (5 × 5 cm) elastomer scaffold whose pores are filled with a self-assembling peptide (SAP) gel entrapping adipose stem cells, to be used as a novel implant in a big animal model (sheep) of myocardial infarction. The study focuses on the way to determine optimal procedures for in...

Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopatho...

Sudden Cardiac Death is a major concern in industrialized countries. In France, it is the cause of death of 40–60,000 cases per year. Despite efforts made over decades to promote cardiac resuscitation science, education, and the arrival of automatic external defibrillators, less than 50 % of cardiac arrest victims are likely to reach recovery of st...

Existing therapies for the treatment of chronic heart failure still have some limitations and there is a pressing need for the development of new therapeutic modalities. The amniotic membrane has been used for the treatment of various diseases, such as con-junctive defects; however, the mechanisms behind its repair functions are still unclear. Rege...

The association of stem cells with tissue-engineered scaffolds constitutes an attractive approach for the repair of myocardial tissue with positive effects to avoid ventricular chamber dilatation, which changes from a natural elliptical to spherical shape in heart failure patients. Biohybrid scaffolds using nanomaterials combined with stem cells em...

Existing therapies for the treatment of chronic heart failure still have some limitations and there is a pressing need for the development of new therapeutic modalities. The amniotic membrane has been used for the treatment of various diseases, such as con-junctive defects; however, the mechanisms behind its repair functions are still unclear. Rege...

Objective: The purpose of this work was to confirm on a pig model the previous work performed on a rabbit model (ReSS 2012) to demonstrate induction of both brain and general hypothermia on a beating heart. Material and method: 8 Landrace pigs 39.4 ± 3.9 kg (mean ± SD) were studied under general anesthesia according to the WICCM protocol. Temperatu...

Ischemic heart disease (IHD) is a leading cause of mortality with insufficient results of current therapies, most probably due to maintained endothelial dysfunction conditions. Alternatively, we propose a new treatment that promotes endothelial shear stress (ESS) enhancement using an intrapulmonary pulsatile catheter. Twelve piglets, divided in equ...

Cardiomyopathy induces geometric alteration of the ventricular cavity, which changes from a natural elliptical (conical) to a spherical shape. Ventricular chamber dilatation and spherical deformation are important causes of morbidity and mortality among patients with congestive heart failure. In addition, diastolic dysfunction is an important clini...

Background: Cardiac-assist devices for right ventricular failure remain controversial with poor results. This study evaluated a pulsatile cardiac-assist device in an acute right ventricular failure model vs. current therapies. Materials and methods: Pulmonary regurgitation was created in 12 piglets by valve avulsion and external transfixation of...

Objectives: Ventricular constraint devices made of polyester and nitinol have been used to treat heart failure patients. Long-term follow-up has not demonstrated significant benefits, probably due to the lack of effects on myocardial tissue and to the risk of diastolic dysfunction. The goal of this experimental study is to improve ventricular cons...

The usefulness of adult stem cells in research and therapeutic applications highly relies on their genomic integrity and stability. Many laboratories including ours have addressed this concern using methods such as karyotyping, Qbanding, fluorescent in situ hybridization, array CGH, flow cytometry and Pap test to evaluate number and structure of ch...

Electrostimulation (ES) can be defined as a safe physical method to induce stem cell differentiation. The aim of this study is to evaluate the effectiveness of ES on bone marrow mesenchymal stem cells (BMSCs) seeded in collagen scaffolds in terms of proliferation and differentiation into cardiomyocytes. BMSCs were isolated from Wistar rats and seed...

Objective Pulmonary arterial hypertension (PAH) is a dysfunctional endothelium disease with increased pulmonary vascular resistance (PVR) and poor prognosis. Current therapies are still insufficient. Here we propose a new pulsatile device as a more effective tool for PAH management compared with traditional treatments. Materials and Methods Twelve...

Adenosine and inosine are both key intracellular energy substrates for nucleotide synthesis by salvage pathways, especially during ischemic stress conditions. Additionally they both possess cell protective and cell repair properties. The objective of this study is to detect potential advantages of the combination of adenosine and inosine versus eac...

Concerning the mechanisms of action, a reduction in mechanical stress seems to contribute to a reduced level of myocardial apoptosis after cardiomyoplasty. Subsequent recurrence of left ventricular dilatation due to detrimental evolution of the underlying myocardial tissue observed in some cases could, in turn, instigate a return to pathological le...

Stem cell therapy, as a strategy to regenerate injured tissues, has emerged as one of the most promising areas for the treatment of illnesses with low possibilities of treatment. The heart failure, mainly of ischemic ethiology, is one of the diseases that more can benefit from this therapeutic strategy. The aim is to regenerate the muscle, reduce a...

Cardiac regeneration requires a complex cascade of events. There are many factors, most of them still no clarified, that limit the effectiveness of the stem cell therapy and their translation to the clinic. Cells should graft, survive and functionally integrate to the target organ in order to have a chance to restore its function. As in original ti...

The stem cell niche, a specialized environment surrounding stem cells, provides crucial support needed for stem cell maintenance. Compromised niche function may lead to the selection of stem cells that no longer depend on self-renewal factors produced by its environment. If the stem cell niche has aged, it might not be capable of supporting the tra...

The incidence of human autologous transplanted skeletal myoblast (SkM) cell death in ischemic myocardium was higher in the first few days after cell therapy. We proposed that human SkM treated by human stromal cell-derived factor (SDF-1α) protein or tranfected by SDF-1α, precondition them against oxidative or anoxic injury. The purification of huma...

Cardiac regeneration requires a complex cascade of events. Stem cell therapy and tissue engineering are newly emerging tools with promising potential for recover or replace of damaged cardiac tissue. There are many factors, most of them still no clarified, that limit the effectiveness of these treatments and their translation to the clinic. Cells s...

Chronic heart failure is one of the major health care issues in terms of increasing number of patients, rate of hospitalizations and costs. Heart transplantation is an excellent approach and a consolidated treatment for these patients. furthermore, the disproportion between the incidence of heart failure and the number of heart donors makes necessa...

ReGeneraTing Agents (RGTAs) are biodegradable polymers engineered to mimic heparan-sulfate in the extracellular matrix of damaged tissue. RGTAs improve tissue healing in several animal models by stabilizing and protecting heparin-binding growth factors and matrix proteins. RGTA restores the normal matrix architecture and supports tissue regeneratio...

The possibility of cell modifications compromises the safety of stem cell therapy under standardized conditions. The aim of this study was to analyze adipose tissue-derived mesenchymal stem cells (AT-MSCs) using the Pap test as a first screening step to evaluate genetic stability. Methods: Human adipose tissue from six healthy female donors was obt...

The knowledge acquired with dynamic cardiomyoplasty has been applied for regenerative cardiology. Stem cell therapy (cellular cardiomyoplasty) for myocardial regeneration in ischemic and non-ischemic cardiomyopathies underwent experimental and clinical evaluations. Myocardial tissue engineering emerges as a new therapeutic tool and extends even mor...

Chronic heart failure is one of the major health care issues in terms of increasing number of patients, rate of hospitalizations and costs. Heart transplantation is the best established therapy for patients with severe heart failure. However, the number of donors limits the activity to 5000 heart transplants performed annually worldwide. This limit...

Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardi...

Background There is mounting evidence to suggest that the heart has regenerative potential in the event of myocardial injury. Recent studies have shown that a resident population of cardiac progenitor cells (CPCs) in the heart contains both vasculogenic and myogenic lineages. CPCs are able to migrate to the site of injury in the heart for participa...

Stem cell therapy is a major field of research worldwide, with increasing clinical application, especially in cardiovascular pathology. However, the best stem cell source and type with optimal safety for functional engraftment remains unclear. An intermediate cardiac precommitted phenotype expressing some of the key proteins of a mature cardiomyocy...

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. Omental flaps in association with growth factors and cell sheets have recently been used to increase the vascularization of ischemic hearts. This experimental study was undertaken to evaluate the hemodynamic evolution and hist...

Experimental studies in animals and recent human clinical trials have revealed the current limitations of cellular transplantation, which include poor cell survival, lack of cell engraftment, and poor differentiation. Evidence in animals suggests that use of a 3-dimensional scaffold may enhance cell therapy and engineer myocardial tissue by improvi...

The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic...

Right heart failure is a frequent hemodynamic disturbance in pediatric cardiac patients. Besides inotropic and chronotropic drugs, fluid administration and inhaled nitric oxide, right ventricular mechanical assistance remains difficult to perform. A circulatory assist device adapted for the right heart biophysics and physiology might be more effici...

Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mon...

Until now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic systol...

Cardiac tissue engineering might be useful in treatment of diseased myocardium or cardiac malformations. The creation of functional, biocompatible contractile tissues, however, remains challenging. We hypothesized that coupling of arginine-glycine-aspartic acid-serine (RGD+) adhesion peptides would improve cardiomyocyte viability and differentiatio...

Myocardial repair using stem-cell therapy has become a promising therapeutic tool. However, many questions concerning a precise functional integration of injected cells remain unanswered. The use of cardiac pre-committed cells may improve integration, as these cells may complete their differentiation in the myocardium reducing fibrosis and restorin...

Las primeras experiencias en la búsqueda de regeneración cardíaca en fase clínica se llevaron a cabo con mioblastos en diversos centros del mundo, entre los que se cuentan instituciones de la República Argentina. Esto motivó en su momento publicaciones en los años 2002 y 2003 sobre los estudios iniciales. Posteriormente se realizó una evaluación de...

The aim of our work was to study the hemodynamic effects of dynamic cardiomyoplasty on an acute animal model of atrial fibrillated heart failure. Eight anesthetized open chest dogs suffering from atrial fibrillation and heart failure, obtained by topic acetylcholine and propranolol, were treated by a cardiomyoplasty procedure performed with an elec...

Atrial fibrillation is the most frequent form of cardiac arrhythmia. Its surgical management has improved in recent years with major advances in our knowledge of the underlying pathogenic mechanisms. This has led to simpler therapeutic strategies such as epicardial ablation. The aim of this comparative experimental study was to evaluate the efficac...

Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis. Seventy male rats were doxorubicin injected intraperiton...

Dynamic cardiomyoplasty (CMP) was proposed as a treatment for refractory heart failure; more than 2000 procedures have been performed worldwide. Heart transplantation was indicated afterwards in some CMP patients with recurrent heart failure symptoms. This study reviews the multicentric French experience with CMP followed by heart transplantation....

La telemonitorización (home monitoring) establece un puente entre el clínico y el paciente por medio de nuevas tecnologías de comunicación. Las aplicaciones actuales de las telemonitorizaciones cardiológicas son: seguimiento continuo de pacientes en insuficiencia cardíaca (medición de frecuencia cardíaca, oximetría, presiones intracardíacas e imped...

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy, the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We eval...

Telemonitoring (home monitoring) builds bridges between clinicians and patients with communication technology. Telemonitoring in cardiology is currently applied in the following situations: follow-up of patients with heart failure (by measuring heart rate, pulse oximetry, intracardiac pressures and pulmonary impedance for diagnosis of pulmonary ede...

The objective of cellular cardiomyoplasty is to regenerate the myocardium using implantation of living cells. Because the extracellular myocardial matrix is deeply altered in ischemic cardiomyopathies, it could be important to create a procedure aiming at regenerating both myocardial cells and the extracellular matrix. We evaluated the potential of...

Objective: Chronically depressed right ventricular (RV) function presents an unresolved therapeutic challenge. Despite recent advances in medical and surgical therapies, prognosis remains poor and patient’s quality of life and mortality are frequently unacceptable. The aim of this work is to present the surgical technique and long-term results of R...

Objectives Cell transplantation for myocardial regeneration is limited by poor graft viability and low cell retention. In addition, in ischemic cardiomyopathy the extracellular matrix is deeply altered. Therefore it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. W...

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evalu...

Mesothelial cells (MCs) are accessible in human patients by excision and digestion of epiploon or from peritoneal fluid or lavage. MCs are easy to culture to obtain large quantities in vitro and they can be genetically modified with interesting therapeutic genes. The important potential of MCs in tissue engineering has been shown during epiplooplas...

We compared two procedures for local myocardial treatment: transepicardial versus transendocardial catheter injection. Transepicardial injections were performed under direct surgical visualization whereas transendocardial injections were performed using electrophysiological guidance. A left ventricle (LV) myocardial infarction (MI) was surgically c...

Ischemic myocardial disease, the main cause of heart failure, is a major public health and economic problem. Given the aging population, heart failure is becoming an increasing clinical issue and a substantial financial burden. Thus, research in heart failure is of relevant interest and importance, involving specialties such as cellular and molecul...

On January 24, 1985, a 37-year-old woman with severe cardiac insufficiency due to a large fibroma (28 x 20 x 10 cm, 1.4 kg) affecting both ventricles and invading the diaphragm, underwent surgery for tumor removal. The residual, thin, multiperforated posterior muscular wall of both ventricles was reinforced by application and suturing of the LDM fl...

El objetivo de la cardiomioplastia celular es regenerar el miocardio mediante el implante de células vivas. Sin embargo, en corazones isquémicos hay alteraciones en la matriz extracelular. El colágeno tipo I, responsable del soporte estructural, disminuye desde el 80% al 40%, mientras que el colágeno tipo III aumenta del 10% al 35%. De esta manera,...

Background: In recent clinical studies, growth factors have been used in both cardio-vascular and plastic surgery. We showed in a previous study that local administration of bFGF (basic Fibroblast Growth Factor), VEGF (vascular endothelial growth factor) and RGTA (regenerating agent), at the Latissimus Dorsi Muscle (LDM)-epicardial interface in a m...

Ventricular dyssynchrony is a relatively common problem in patients with heart failure, in particular those with wide QRS complex, and appears to have a deleterious effect on the natural history of heart failure, as it has been associated with increased mortality. Mechanistic studies, observational evaluations, and randomized trials have consistent...