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1.
Tissue Eng Part C Methods ; 25(8): 500-511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31337288

RESUMO

IMPACT STATEMENT: Polymorphonuclear leukocytes (PMNs) are essential in the first infection and host-versus-graft reactions. Strategies for adequate and standardized assays to test PMN activation by diverse types of matrices such as cardiovascular implants are urgently needed. To overcome this limitation, we established a straightforward PMN activation assay and validated lipopolysaccharide (LPS) as a reliable PMN activator that induces defined changes in surface marker expression and cytokine release. Biological "proof-of-principle" matrices demonstrated the feasibility of this PMN assay. Overall, this assay provides an instrument conducting an initial immunological assessment of biological implants prior their clinical application.

2.
Ther Adv Cardiovasc Dis ; 13: 1753944719841795, 2019 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31088231

RESUMO

BACKGROUND: Pressure-overload left-ventricular hypertrophy (LVH) is an increasingly prevalent pathological condition of the myocardial muscle and an independent risk factor for a variety of cardiac diseases. We investigated changes in expression levels of proangiogeneic genes in a small animal model of LVH. METHODS: Myocardial hypertrophy was induced by transaortic constriction (TAC) in C57BL/6 mice and compared with sham-operated controls. The myocardial expression levels of vascular endothelial growth factor (VEGF), its receptors (KDR and FLT-1), stromal-cell-derived factor 1 (SDF1) and the transcription factors hypoxia-inducible factor-1 and 2 (HIF1 and HIF2) were analyzed by quantitative polymerase chain reaction over the course of 25 weeks. Histological sections were stained for caveolin-1 to visualize endothelial cells and determine the capillary density. The left-ventricular morphology and function were assessed weekly by electrocardiogram-gated magnetic resonance imaging. RESULTS: The heart weight of TAC animals increased significantly from week 4 to 25 ( p = 0.005) compared with sham-treated animals. At 1 day after TAC, the expression of VEGF and SDF1 also increased, but was downregulated again after 1 week. The expression of HIF2 was significantly downregulated after 1 week and remained at a lower level in the subsequent weeks. The expression level of FLT-1 was also significantly decreased 1 week after TAC. HIF-1 and KDR showed similar changes compared with sham-operated animals. However, the expression levels of HIF1 after 4 and 8 weeks were significantly decreased compared with day 1. KDR changes were significantly decreased after 1, 2, 4, 8 and 25 weeks compared with week 3. After 4 weeks post-TAC, the size of the capillary vessels increased ( p = 0.005) while the capillary density itself decreased (TAC: 2143 ± 293 /mm2 versus sham: 2531 ± 321 /mm2; p = 0.021). Starting from week 4, the left-ventricular ejection fraction decreased compared with controls ( p = 0.049). CONCLUSIONS: The decrease in capillary density in the hypertrophic myocardium appears to be linked to the dysregulation in the expression of proangiogeneic factors. The results suggest that overcoming this dysregulation may lead to reconstitution of capillary density in the hypertrophic heart, and thus be beneficial for cardiac function and survival.


Assuntos
Proteínas Angiogênicas/metabolismo , Capilares/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Miocárdio/metabolismo , Neovascularização Fisiológica , Proteínas Angiogênicas/genética , Animais , Capilares/patologia , Capilares/fisiopatologia , Técnicas de Imagem de Sincronização Cardíaca , Modelos Animais de Doenças , Eletrocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Imagem por Ressonância Magnética , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Transdução de Sinais , Fatores de Tempo , Função Ventricular Esquerda , Remodelação Ventricular
3.
J Mol Cell Cardiol ; 131: 53-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005484

RESUMO

AIMS: Atrial contractile dysfunction is associated with increased mortality in heart failure (HF). We have shown previously that a metabolic syndrome-based model of HFpEF and a model of hypertensive heart disease (HHD) have impaired left atrial (LA) function in vivo (rat). In this study we postulate, that left atrial cardiomyocyte (CM) and cardiac fibroblast (CF) paracrine interaction related to the inositol 1,4,5-trisphosphate signalling cascade is pivotal for the manifestation of atrial mechanical dysfunction in HF and that quantitative atrial remodeling is highly disease-dependent. METHODS AND RESULTS: Differential remodeling was observed in HHD and HFpEF as indicated by an increase of atrial size in vivo (HFpEF), unchanged fibrosis (HHD and HFpEF) and a decrease of CM size (HHD). Baseline contractile performance of rat CM in vitro was enhanced in HFpEF. Upon treatment with conditioned medium from their respective stretched CF (CM-SF), CM (at 21 weeks) of WT showed increased Ca2+ transient (CaT) amplitudes related to the paracrine activity of the inotrope endothelin (ET-1) and inositol 1,4,5-trisphosphate induced Ca2+ release. Concentration of ET-1 was increased in CM-SF and atrial tissue from WT as compared to HHD and HFpEF. In HHD, CM-SF had no relevant effect on CaT kinetics. However, in HFpEF, CM-SF increased diastolic Ca2+ and slowed Ca2+ removal, potentially contributing to an in-vivo decompensation. During disease progression (i.e. at 27 weeks), HFpEF displayed dysfunctional excitation-contraction-coupling (ECC) due to lower sarcoplasmic-reticulum Ca2+ content unrelated to CF-CM interaction or ET-1, but associated with enhanced nuclear [Ca2+]. In human patients, tissue ET-1 was not related to the presence of arterial hypertension or obesity. CONCLUSIONS: Atrial remodeling is a complex entity that is highly disease and stage dependent. The activity of fibrosis related to paracrine interaction (e.g. ET-1) might contribute to in vitro and in vivo atrial dysfunction. However, during later stages of disease, ECC is impaired unrelated to CF.

5.
Atherosclerosis ; 284: 230-236, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30777338

RESUMO

BACKGROUND AND AIMS: Density may indicate some tissue characteristics and help reveal the role of epicardial adipose tissue (EAT) in coronary artery disease (CAD). Therefore, we assessed the association of EAT density with the coronary artery plaque burden in patients presenting with chest pain. METHODS: This retrospective cohort study comprised 614 patients (mean age 61 ±â€¯9 years, 61% males) with a high cardiovascular disease risk, who underwent cardiac computed tomography angiography. Density was reflected as attenuation. RESULTS: EAT attenuation was significantly associated with EAT volume with a negative Pearson's correlation coefficient and gradually increased across coronary artery calcium (CAC) scores of 0, 1-100, 101-400 and > 400. EAT attenuation was tightly associated with CAD risk factors, including age, sex, BMI, total cholesterol, neutrophil to lymphocyte ratios and CAC score. The association between EAT attenuation and CAC score was strengthened after adjusting for multivariable indices (OR 1.21, 95% CI 1.05-1.40, p = 0.01) and further adjusting for EAT volume (OR 1.26 95% CI 1.06-1.51, p<0.01). However, EAT attenuation was associated only with CAD presence (OR 1.32, 95% CI 1.02-1.69, p<0.05), CAC presence (OR 1.28, 95% CI 1.02-1.60, p<0.05), segment involvement score (OR 1.19, 95% CI 1.01-1.40, p<0.05) and segment stenosis score (OR 1.19, 95% CI 1.01-1.40, p<0.05) in the EAT volume- and multivariable-adjusted model. Additionally, EAT attenuation was not associated with significant coronary artery lesions and triple-vessel plaques. CONCLUSIONS: Higher EAT attenuation is associated with a higher risk of CAD.

6.
Cell Mol Life Sci ; 76(9): 1681-1695, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30721319

RESUMO

Despite significant developments in medical and surgical strategies, cardiac diseases remain the leading causes of morbidity and mortality worldwide. Numerous studies involving preclinical and clinical trials have confirmed that stem cell transplantation can help improve cardiac function and regenerate damaged cardiac tissue, and stem cells isolated from bone marrow, heart tissue, adipose tissue and umbilical cord are the primary candidates for transplantation. During the past decade, menstrual blood-derived endometrial stem cells (MenSCs) have gradually become a promising alternative for stem cell-based therapy due to their comprehensive advantages, which include their ability to be periodically and non-invasively collected, their abundant source material, their ability to be regularly donated, their superior proliferative capacity and their ability to be used for autologous transplantation. MenSCs have shown positive therapeutic potential for the treatment of various diseases. Therefore, aside from a brief introduction of the biological characteristics of MenSCs, this review focuses on the progress being made in evaluating the functional improvement of damaged cardiac tissue after MenSC transplantation through preclinical and clinical studies. Based on published reports, we conclude that the paracrine effect, transdifferentiation and immunomodulation by MenSC promote both regeneration of damaged myocardium and improvement of cardiac function.


Assuntos
Reabilitação Cardíaca/métodos , Doenças Cardiovasculares/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Endométrio/citologia , Transplante de Células-Tronco , Células-Tronco/citologia , Adulto , Idoso , Transdiferenciação Celular/fisiologia , Feminino , Humanos , Masculino , Menstruação/sangue , Adulto Jovem
7.
Lancet Respir Med ; 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30274956

RESUMO

BACKGROUND: The large amount of clinical signals in intensive care units can easily overwhelm health-care personnel and can lead to treatment delays, suboptimal care, or clinical errors. The aim of this study was to apply deep machine learning methods to predict severe complications during critical care in real time after cardiothoracic surgery. METHODS: We used deep learning methods (recurrent neural networks) to predict several severe complications (mortality, renal failure with a need for renal replacement therapy, and postoperative bleeding leading to operative revision) in post cardiosurgical care in real time. Adult patients who underwent major open heart surgery from Jan 1, 2000, to Dec 31, 2016, in a German tertiary care centre for cardiovascular diseases formed the main derivation dataset. We measured the accuracy and timeliness of the deep learning model's forecasts and compared predictive quality to that of established standard-of-care clinical reference tools (clinical rule for postoperative bleeding, Simplified Acute Physiology Score II for mortality, and the Kidney Disease: Improving Global Outcomes staging criteria for acute renal failure) using positive predictive value (PPV), negative predictive value, sensitivity, specificity, area under the curve (AUC), and the F1 measure (which computes a harmonic mean of sensitivity and PPV). Results were externally retrospectively validated with 5898 cases from the published MIMIC-III dataset. FINDINGS: Of 47 559 intensive care admissions (corresponding to 42 007 patients), we included 11 492 (corresponding to 9269 patients). The deep learning models yielded accurate predictions with the following PPV and sensitivity scores: PPV 0·90 and sensitivity 0·85 for mortality, 0·87 and 0·94 for renal failure, and 0·84 and 0·74 for bleeding. The predictions significantly outperformed the standard clinical reference tools, improving the absolute complication prediction AUC by 0·29 (95% CI 0·23-0·35) for bleeding, by 0·24 (0·19-0·29) for mortality, and by 0·24 (0·13-0·35) for renal failure (p<0·0001 for all three analyses). The deep learning methods showed accurate predictions immediately after patient admission to the intensive care unit. We also observed an increase in performance in our validation cohort when the machine learning approach was tested against clinical reference tools, with absolute improvements in AUC of 0·09 (95% CI 0·03-0·15; p=0·0026) for bleeding, of 0·18 (0·07-0·29; p=0·0013) for mortality, and of 0·25 (0·18-0·32; p<0·0001) for renal failure. INTERPRETATION: The observed improvements in prediction for all three investigated clinical outcomes have the potential to improve critical care. These findings are noteworthy in that they use routinely collected clinical data exclusively, without the need for any manual processing. The deep machine learning method showed AUC scores that significantly surpass those of clinical reference tools, especially soon after admission. Taken together, these properties are encouraging for prospective deployment in critical care settings to direct the staff's attention towards patients who are most at risk. FUNDING: No specific funding.

8.
FASEB J ; : fj201800712R, 2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30188756

RESUMO

To date, no viable therapeutic options exist for the effective and sustained reversal of cardiac failure, other than heart transplantation and mechanical circulatory assist devices. Therefore, divergent strategies aiming at the de novo formation of contractile tissue, as a prerequisite for the restoration of cardiac pump function, are currently being pursued. Clinical trials involving the transplantation of somatic progenitor cells failed. The search for alternative cell-based strategies to combat the consequences of ischemic injury has sparked widespread interest in the genetic and pharmacologic reprogramming of fibroblasts into cardiomyocytes, harnessing the abundant in vivo pool of cardiac fibroblasts. Here, we provide a comprehensive overview of in vitro and in vivo cardiac reprogramming studies identified in an extensive literature search. We systematically review and evaluate feasibility, efficiency, and reproducibility of the different technologies currently being explored. Finally, we discuss potential safety issues deduced from preclinical studies and identify obstacles that must be overcome before clinical translation.-Klose, K., Gossen, M., Stamm, C. Turning fibroblasts into cardiomyocytes: technological review of cardiac transdifferentiation strategies.

10.
Innovations (Phila) ; 13(3): 230-232, 2018 May/Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29916851

RESUMO

A 58-year-old white male with a history of stroke and deep vein thrombosis presented with an interatrial intraseptal mass. Cardiac-computed tomography demonstrated a thin-walled, well-demarcated cyst in the inferior border of the fossa ovalis protruding into both atria. Removal of the interatrial intraseptal cyst was performed using a minimally invasive three-dimensional endoscopic periareolar approach.

11.
Stem Cells Int ; 2018: 5832460, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760728

RESUMO

Despite regulatory issues surrounding the use of animal-derived cell culture supplements, most clinical cardiac cell therapy trials using mesenchymal stromal cells (MSCs) still rely on fetal bovine serum (FBS) for cell expansion before transplantation. We sought to investigate the effect of human serum from heart failure patients (HFS) on cord blood MSCs (CB-MSCs) during short-term culture under regular conditions and during simulated acute and chronic stress. Cell survival, proliferation, metabolic activity, and apoptosis were quantified, and gene expression profiles of selected apoptosis and cell cycle regulators were determined. Compared to FBS, HFS and serum from healthy donors (CS) showed similar effects by substantially increasing cell survival during chronic and acute stress and by increasing cell yields 5 days after acute stress. Shortly after the termination of acute stress, both HFS and CS resulted in a marked decrease in apoptotic cells. Transcriptome analysis suggested a decrease in TNF-mediated induction of caspases and decreased activation of mitochondrial apoptosis. Our data confirm that human serum from both healthy donors and heart failure patients results in increased cell yields and increased resistance to cellular stress signals. Therefore, we consider autologous serum a valid alternative to FBS in cell-based therapies addressing severe heart disease.

12.
Interv Cardiol ; 13(1): 14-19, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29593831

RESUMO

Minimally invasive surgical mitral valve repair (MVRepair) has become routine for the treatment of mitral valve regurgitation, and indications have been expanded to include reoperations. Current European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines for the management of valvular heart disease recommended standards in terms of mitral valve disease differentiation, timing of intervention and surgical techniques to improve patient care. Numerous minimally invasive techniques to lessen the invasiveness have been described, such as the minimal-access J-sternotomy (ministernotomy), the parasternal incision, the port-access technique and the right minithoracotomy. Despite the development of catheter-based techniques, surgical repair remains the gold standard today for nearly all patients with degenerative valvular diseases and the majority of patients with other types of valvular diseases. Techniques include resection of the prolapsed segment, neo-chordae implantation and ring annuloplasty. In this review, the current indications for mitral valve surgery are summarised and state-of-the-art MVRepair techniques are highlighted.

13.
Int J Mol Sci ; 19(4)2018 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-29596384

RESUMO

There is a growing need for scaffold material with tissue-specific bioactivity for use in regenerative medicine, tissue engineering, and for surgical repair of structural defects. We developed a novel composite biomaterial by processing human cardiac extracellular matrix (ECM) into a hydrogel and combining it with cell-free amniotic membrane via a dry-coating procedure. Cardiac biocompatibility and immunogenicity were tested in vitro using human cardiac fibroblasts, epicardial progenitor cells, murine HL-1 cells, and human immune cells derived from buffy coat. Processing of the ECM preserved important matrix proteins as demonstrated by mass spectrometry. ECM coating did not alter the mechanical characteristics of decellularized amniotic membrane but did cause a clear increase in adhesion capacity, cell proliferation and viability. Activated monocytes secreted less pro-inflammatory cytokines, and both macrophage polarization towards the pro-inflammatory M1 type and T cell proliferation were prevented. We conclude that the incorporation of human cardiac ECM hydrogel shifts and enhances the bioactivity of decellularized amniotic membrane, facilitating its use in future cardiac applications.


Assuntos
Âmnio/química , Matriz Extracelular/química , Hidrogéis/química , Teste de Materiais , Miocárdio/química , Tecidos Suporte/química , Adesão Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Humanos
14.
Thorac Cardiovasc Surg ; 66(1): 53-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29216651

RESUMO

For more than 20 years, tremendous efforts have been made to develop cell-based therapies for treatment of heart failure. However, the results of clinical trials using somatic, nonpluripotent stem or progenitor cells have been largely disappointing in both cardiology and cardiac surgery scenarios. Surgical groups were among the pioneers of experimental and clinical myocyte transplantation ("cellular cardiomyoplasty"), but little translational progress was made prior to the development of cellular reprogramming for creation of induced pluripotent stem cells (iPSC). Ever since, protocols have been developed which allow for the derivation of large numbers of autologous cardiomyocytes (CMs) from patient-specific iPSC, moving translational research closer toward clinical pilot trials. However, compared with somatic cell therapy, the technology required for safe and efficacious pluripotent stem cell (PSC)-based therapies is extremely complex and requires tremendous resources and close interactions between basic scientists and clinicians. This review summarizes PSC sources, strategies to derive CMs, current cardiac tissue engineering approaches, concerns regarding immunogenicity and cellular maturity, and highlights the contributions made by surgical groups.


Assuntos
Doenças Cardiovasculares/cirurgia , Células-Tronco Embrionárias/transplante , Miocárdio/patologia , Miócitos Cardíacos/transplante , Células-Tronco Pluripotentes/transplante , Regeneração , Medicina Regenerativa/métodos , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Linhagem da Célula , Reprogramação Celular , Técnicas de Reprogramação Celular , Células-Tronco Embrionárias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/transplante , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fenótipo , Células-Tronco Pluripotentes/metabolismo , Recuperação de Função Fisiológica , Transdução de Sinais , Resultado do Tratamento
15.
Thorac Cardiovasc Surg ; 66(1): 42-52, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29284167

RESUMO

Preclinical data suggested that somatic stem or progenitor cells derived induce and/or support endogenous repair mechanisms of the myocardium. Such cell populations were clearly shown to promote neovascularization in postischemic tissue, and some evidence also indicated transdifferentiation into cardiomyocytes. In the clinical setting, however, many attempts to regenerate damaged myocardium with a variety of autologous and allogeneic somatic progenitors have failed to generate the expected therapeutic efficacy. Currently, efforts are being made to select specific cellular subpopulations, modify somatic cells to augment their regenerative capacity, improve delivery methods, and develop markers selection of potentially responding patients. Cardiac surgical groups have pioneered and continue to advance the field of cellular therapies. While the initial excitement has subsided, the field has evolved into one of the pillars of surgical research and benefits from novel methods such as cellular reprogramming, genetic modification, and pluripotent stem cell technology. This review highlights developments and controversies in somatic cardiac cell therapy and provides a comprehensive overview of completed and ongoing clinical trials.


Assuntos
Células-Tronco Adultas/transplante , Transplante de Medula Óssea , Doenças Cardiovasculares/cirurgia , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Mioblastos Esqueléticos/transplante , Miocárdio/patologia , Regeneração , Medicina Regenerativa/métodos , Células-Tronco Adultas/metabolismo , Animais , Transplante de Medula Óssea/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Diferenciação Celular , Linhagem da Célula , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Mioblastos Esqueléticos/metabolismo , Miocárdio/metabolismo , Fenótipo , Recuperação de Função Fisiológica , Transdução de Sinais , Resultado do Tratamento
16.
J Tissue Eng Regen Med ; 12(3): e1404-e1417, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28752609

RESUMO

Cardiac-derived adherent proliferating (CardAP) cells obtained from endomyocardial biopsies (EMBs) with known anti-fibrotic and pro-angiogenic properties are good candidates for the autologous therapy of end-stage cardiac diseases such as dilated cardiomyopathy. However, due to the limited number of CardAP cells that can be obtained from EMBs, our aim is to isolate cells with similar properties from other regions of the heart with comparable tissue architecture. Here, we introduce the atrial appendage as a candidate region. Atrial appendage-derived cells were sorted with CD90 microbeads to obtain a CD90low cell population, which were subsequently analysed for their surface marker and gene expression profiles via flow cytometry and micro array analysis. Enzyme-linked immunosorbent assays for vascular endothelial growth factor and interleukin-8 as well as tube formation assays were performed to investigate pro-angiogenic properties. Furthermore, growth kinetic assays were performed to estimate the cell numbers needed for cell-based products. Microarray analysis revealed the expression of numerous pro-angiogenic genes and strong similarities to CardAP cells with which they also share expression levels of defined surface antigens, that is, CD29+ , CD44+ , CD45- , CD73+ , CD90low , CD105+ , and CD166+ . High secretion levels of vascular endothelial growth factor and interleukin-8 as well as improved properties of vascular structures in vitro could be detected. Based on growth parameters, cell dosages for the treatment of more than 250 patients are possible using one appendage. These results lead to the conclusion that isolating cells with regenerative characteristics from atrial appendages is feasible and permits further investigations towards allogenic cell-based therapies.

17.
Expert Rev Cardiovasc Ther ; 16(2): 75-89, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29283684

RESUMO

INTRODUCTION: Tricuspid valve regurgitation (TR) is frequently encountered and is most often functional (FTR) in nature. Surgical tricuspid valve (TV) treatment is well established in specialized centers. While transcatheter therapy for other valve disease is well established, interventional treatment of TV disease is still in its early stages. With the increasing adoption of catheter-based treatments, there is a growing interest in and need for interventional treatments for TR. An extensive literature search was methodologically performed aiming for an integrative review paper. Areas covered: This review will discuss the current surgical treatment modalities and emerging transcatheter interventions in the management of TR. Furthermore, this review will describe the pathophysiology of functional tricuspid regurgitation (FTR), and the new 2017 ESC/EACTS guidelines for the management of TR. Finally, a five-year view into the future will be stated. Expert commentary: At their center, the authors have an aggressive approach for the treatment of FTR owing to its significant impact on perioperative as well as late postoperative morbidity and mortality. The authors perform TV ring annuloplasty when substantial annular dilation (≥45mm) is observed. In the future, percutaneous TV technologies might become an alternative option to treat TR patients with high surgical risk selectively.


Assuntos
Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Doenças das Valvas Cardíacas/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Resultado do Tratamento , Insuficiência da Valva Tricúspide/fisiopatologia
18.
J Vis Exp ; (130)2017 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-29286394

RESUMO

Acellular extracellular matrix preparations are useful for studying cell-matrix interactions and facilitate regenerative cell therapy applications. Several commercial extracellular matrix products are available as hydrogels or membranes, but these do not possess tissue-specific biological activity. Because perfusion decellularization is usually not possible with human heart tissue, we developed a 3-step immersion decellularization process. Human myocardial slices procured during surgery are first treated with detergent-free hyperosmolar lysis buffer, followed by incubation with the ionic detergent, sodium dodecyl sulfate, and the process is completed by exploiting the intrinsic DNase activity of fetal bovine serum. This technique results in cell-free sheets of cardiac extracellular matrix with largely preserved fibrous tissue architecture and biopolymer composition, which were shown to provide specific environmental cues to cardiac cell populations and pluripotent stem cells. Cardiac extracellular matrix sheets can then be further processed into a microparticle powder without further chemical modification, or, via short-term pepsin digestion, into a self-assembling cardiac extracellular matrix hydrogel with preserved bioactivity.


Assuntos
Hidrogel de Polietilenoglicol-Dimetacrilato/química , Miócitos Cardíacos/citologia , Engenharia Tecidual/métodos , Matriz Extracelular/química , Humanos
19.
Sci Rep ; 7(1): 17027, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29208929

RESUMO

Conventional frozen cryopreservation (CFC) is currently the gold standard for cardiovascular allograft preservation. However, inflammation and structural deterioration limit transplant durability. Ice-free cryopreservation (IFC) already demonstrated matrix structure preservation combined with attenuated immune responses. In this study, we aim to explore the mechanisms of this diminished immunogenicity in vitro. First, we characterized factors released by human aortic tissue after CFC and IFC. Secondly, we analyzed co-cultures with human peripheral blood mononuclear cells, purified monocytes, T cells and monocyte-derived macrophages to examine functional immune effects triggered by the tissue or released cues. IFC tissue exhibited significantly lower metabolic activity and release of pro-inflammatory cytokines than CFC tissue, but surprisingly, more active transforming growth factor ß. Due to reduced cytokine release by IFC tissue, less monocyte and T cell migration was detected in a chemotaxis system. Moreover, only cues from CFC tissue but not from IFC tissue amplified αCD3 triggered T cell proliferation. In a specifically designed macrophage-tissue assay, we could show that macrophages did not upregulate M1 polarization markers (CD80 or HLA-DR) on either tissue type. In conclusion, IFC selectively modulates tissue characteristics and thereby attenuates immune cell attraction and activation. Therefore, IFC treatment creates improved opportunities for cardiovascular graft preservation.

20.
Am J Cardiol ; 120(12): 2247-2255, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29103606

RESUMO

Transcatheter aortic valve implantation shortcomings such as relevant paravalvular leakage (PVL) have been shown to negatively impact survival. The Sapien 3 prosthesis has added features to address these problems. We compared the functional performance of the Sapien 3 (S3) and its predecessor Sapien XT (XT), with a particular focus on PVL. We analyzed 601 patients presenting with severe native aortic valve stenosis treated with either Sapien XT (n = 405, 2011 to 2014, mean STS-PROM [Society of Thoracic Surgeons predicted risk of mortality] 11.0%) or Sapien 3 prosthesis (n = 196, 2014 to 2016, mean STS-PROM 9.2%). Beside a propensity score-based comparison, we modeled the likelihood of PVL as a function of oversizing and prosthesis. Primary end points were 1-year survival, degree of oversizing, and occurrence of PVL. One-year survival (stratified log-rank p = 1.00) and 30-day mortality (S3: 10 of 126 vs XT: 10 of 126, p = 1.00) did not differ. In the matched cohort, oversizing was less common in the S3 group (absolute median difference of 7% in oversizing, interquartile range 1.1% to 12.7%, p = 0.025). PVL > = 1° was similar in both groups (S3: 13 of 126 vs XT: 20 of 126, p = 0.296). Mean gradients were lower in the XT group (median difference 1.0 mm Hg, interquartile range 0.3 to 1.8 mm Hg, p = 0.005). Rate of postdilatation, implantation of a second valve (valve-in-valve), annular rupture, and new pacemaker implantation were similar (all p = 1.00). In conclusion, compared with the Sapien XT, the redesigned Sapien 3 prosthesis offers effective sealing against PVL without grossly compromising hemodynamic performance or increasing the necessity for new pacemaker implantation.


Assuntos
Estenose da Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Tomografia Computadorizada Multidetectores , Complicações Pós-Operatórias/diagnóstico , Pontuação de Propensão , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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