Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Trial): Clinical Feasibility Study

Chachques, Juan Carlos; Trainini, Jorge C.; Lago, Noemí; Cortés-Morichetti, Miguel; Schussler, Olivier; Carpentier, Alain

doi:10.1016/j.athoracsur.2007.10.052

Cited by 176 publications

(130 citation statements)

References 45 publications

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“…[1][2][3] Although regenerative therapies, such as gene and cell therapies, have been under development to suppress worsening heart failure, 39,40 most of them are invasive in nature, and their efficacy and safety have not been established yet. [41][42][43] Because the intensity of ultrasound used in the LIPUS therapy is below the upper limit of acoustic output standards for diagnostic ultrasound devices, the therapy does not cause compression, heat, or discomfort. For this noninvasive nature, our LIPUS therapy can be used as an adjunctive therapy in patients with AMI to suppress post-MI LV remodeling.…”

Section: Discussionmentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

Shindo

Ito

Ogata

et al. 2016

ATVB

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Objective-Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. Approach and Results-We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. Conclusions-These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved. (Arterioscler Thromb Vasc

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Section: Discussionmentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

Shindo

Ito

Ogata

et al. 2016

ATVB

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“…Single truncahedrons and more complex structures of different size could be produced within the same technological approach [21]. The pore size of the scaffold has to be about twice as big as the size of a single cell, and for mammals it would correspond to tens of micrometres [33]. Precise control of pore sizes, their homogeneity and interconnection is believed to be beneficial for cell proliferation [34].…”

Section: Fabrication Of 3d Artificial Scaffoldsmentioning

confidence: 99%

3D artificial polymeric scaffolds for stem cell growth fabricated by femtosecond laser

Malinauskas

Danilevičius²,

Baltriukienė³

et al. 2010

Lithuanian J. Phys.

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Femtosecond Laser Induced Polymerization is an attractive direct writing technique for rapid three-dimensional (3D) micro and nanofabrication in diverse applications. Recently, it has been successfully applied for 3D scaffold fabrication required in biomedicine applications. However, there are still a lot of investigations to be done before it can be used for practical applications in tissue engineering or regenerative medicine. In this work, experimental results on production of artificial polymeric scaffolds for stem cell growth are presented. Parameters (average laser power, sample scanning speed, and developing conditions) for microfabrication in biocompatible photopolymers AKRE (AKRE37) and ORMOSIL (SZ2080) are experimentally determined. 3D custom form and size artificial scaffolds were successfully microfabricated. Adult stem cell growth on them was investigated in order to test their biocompatibility. The results of myogenic stem cell culture expansion were compared to the control growth of the same cells on the scaffolds manufactured out of commonly used biocompatible photopolymers ORMOCER (Ormocore b59) and Poly-Ethylen Glycol Di-Acrylate (PEG-DA-258). Preliminary results show FLIP technique to have potential in fabrication of artificial 3D polymeric scaffolds for cell proliferation experiments. These are the first steps in transferring FLIP fabrication method from laboratory tests to flexible manufacturing of individual scaffolds out of biocompatible and biodegradable polymers.

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“…Cell delivery methods are progressing through clinical trials, particularly in the setting of end-stage heart failure, where the lack of effective therapies leads to more than 500,000 deaths per year in the United States alone (4). Human mesenchymal stem cells (MSCs) were used with variable functional improvement and neovascularization (5)(6)(7)(8)(9)(10). This outcome is thought to be largely due to the use of cell suspensions that are limited by poor cell retention (11), survival (12), engraftment (13), and differentiation (14).…”

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confidence: 99%

Composite scaffold provides a cell delivery platform for cardiovascular repair

Godier-Furnémont

Martens

Koeckert

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

234

203

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Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cellmatrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.biomaterial | cardiac repair | human stem cell | cardiac patch G iven the adult heart's minimal capacity for endogenous regeneration (1), cell therapy has emerged as a viable option for revascularization (2) and regeneration (3) of the infarct bed. Cell delivery methods are progressing through clinical trials, particularly in the setting of end-stage heart failure, where the lack of effective therapies leads to more than 500,000 deaths per year in the United States alone (4). Human mesenchymal stem cells (MSCs) were used with variable functional improvement and neovascularization (5-10). This outcome is thought to be largely due to the use of cell suspensions that are limited by poor cell retention (11), survival (12), engraftment (13), and differentiation (14). The underlying mechanisms (i.e., secretion of paracrine factors vs. cell incorporation) are not well defined and can be interrogated only through control over cell retention (e.g., by the use of scaffolding materials) and insight into cell phenotype (e.g., expression of functional markers). We introduce a cell delivery platform that combines a fully biological gel-matrix composite scaffold with biochemical preconditioning of human MPCs. The resulting vasculogenic and myogenic cell properties and functional benefits of the cell delivery platform were evaluated in an animal model of myocardial infarction (MI). Results and DiscussionCell Delivery Platform. Composite scaffolds for cell delivery were assembled from thin sheets of decellularized human myocardium and fibrin hydrogel. MPCs were imm...

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Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Trial): Clinical Feasibility Study

Cited by 176 publications

References 45 publications

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

3D artificial polymeric scaffolds for stem cell growth fabricated by femtosecond laser

Composite scaffold provides a cell delivery platform for cardiovascular repair

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