Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction

Gaetani, Roberto; Feyen, Dries; Verhage, Vera; Slaats, Rolf H.; Messina, Elisa; Christman, Karen L.; Giacomello, Alessandro; Doevendans, Pieter A.; Sluijter, Joost P.G.

doi:10.1016/j.biomaterials.2015.05.005

Cited by 278 publications

(201 citation statements)

References 39 publications

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“…Myocardial regeneration likely requires not only a "regenerative" matrix profile, but also local secretion of a yet-undefined combination of cytokines and growth factors, and activation of pathways that enhance plasticity of progenitor cell populations (146). Third, in several cell therapy studies in mammalian models of cardiac injury, application of matrix-based patches containing progenitor cells showed enhanced effectiveness (147,148). It has been suggested that application of matrix patches that recapitulate the regenerative environment of the embryonic myocardium may increase TSP-1, may drive the fate of cardiac interstitial cells toward a fibroblast phenotype promoting fibrotic remodeling.…”

Section: The Cardiac Ecm In Metabolic Diseasementioning

confidence: 99%

The extracellular matrix in myocardial injury, repair, and remodeling

Frangogiannis¹

2017

Journal of Clinical Investigation

400

318

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Section: The Cardiac Ecm In Metabolic Diseasementioning

confidence: 99%

The extracellular matrix in myocardial injury, repair, and remodeling

Frangogiannis¹

2017

Journal of Clinical Investigation

400

318

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“…Cardiac and subcutaneous adipose tissue‐derived progenitor cells can differentiate into cardiomyocytes and endothelial cells when loading onto a fibrin patch 15. Three‐dimensional‐printed gelatin/hyaluronic acid patch carrying cardiac‐derived progenitor cells reduces adverse cardiac remodelling and preserves cardiac performance, and the matrix supports engraftment and survival of the cells 16. Our early study suggested that poly(ɛ‐caprolactone) (PCL)/gelatin patch may effectively restrict the expansion of the infarcted ventricular wall and that patch‐delivered bone marrow‐derived MSCs promote angiogenesis and repair of the infarcted myocardium 17.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Wang

et al. 2017

J Cellular Molecular Medi

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Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF‐1α, Tβ4, VEGF and SDF‐1 expression and decreased CXCL14 expression in hypoxic and serum‐deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF‐1α, Tβ4, VEGF, SDF‐1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial‐derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c‐kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

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“…After being administered, cells can be nearly gone as soon as 1 to 3 days after transplantation [44,45]. However, some authors reported signs of stem cell survival up to 1 week [8,16,60,100,104], 1 month [14,18,23,27,30,37,46,52,67,105] and, most strikingly, up to 1 year [26]. When retained cells are quantified, we find that less than 3% of the stem cells survive more than 4 weeks [59,70] and that percentage drops to levels below 1% when the assessment is made 16 weeks after transplantation [106].…”

Section: Mechanistic Challengesmentioning

confidence: 99%

“…The final, yet the most compromising, issue in clinical translation is related to the therapy monitoring, particularly the molecular analysis, which is performed post-mortem in animal models by, for instance, histological and immunohistochemical analysis as well as by PCR and western blot techniques making use of heart tissue samples [3,8,15,16,21,22,29,34,38,41,51,54,61,62,64,105,109,110,119]. Only Chen et al [103].…”

Section: Clinical Translationmentioning

confidence: 99%

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Trindade

Leite‐Moreira

Ferreira-Martins

et al. 2017

International Journal of Cardiology

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Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

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Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction

Cited by 278 publications

References 39 publications

The extracellular matrix in myocardial injury, repair, and remodeling

The extracellular matrix in myocardial injury, repair, and remodeling

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

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