RESUMEN
There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with those from E14.5 embryos. Our results indicate that tail-vein-infused E11.5 ventricular cells are more efficient at homing into the injured adult myocardium, and are more angiogenic, than E14.5 ventricular cells. In addition, E11.5 cells were shown to mitigate the cardiomyopathic effects of Dox. In vitro, E11.5 ventricular cells were more migratory than E14.5 cells, and RT-qPCR analysis revealed that they express significantly higher levels of cytokine receptors Fgfr1, Fgfr2, Pdgfra, Pdgfrb and Kit. Remarkably, mRNA levels for Fgf1, Fgf2, Pdgfa and Pdgfb were also found to be elevated in the Dox-injured adult heart, as were the FGF1 and PDGFB protein levels. Addition of exogenous FGF1 or PDGFB was able to enhance E11.5 ventricular cell migration in vitro, and, whereas their neutralizing antibodies decreased cell migration. These results indicate that therapies raising the levels of FGF1 and PDGFB receptors in donor cells and or corresponding ligands in an injured heart could improve the efficacy of cell-based interventions for myocardial repair.
Asunto(s)
Trasplante de Células , Doxorrubicina/efectos adversos , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Miocardio/patología , Proteínas Proto-Oncogénicas c-sis/metabolismo , Envejecimiento/genética , Animales , Movimiento Celular , Electrocardiografía , Embrión de Mamíferos/patología , Regulación de la Expresión Génica , Ventrículos Cardíacos/embriología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/trasplante , Ratones Endogámicos C57BL , Neovascularización Fisiológica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismoRESUMEN
BACKGROUND: The optimal surgical management of patients with transposition of the great arteries (TGA), ventricular septal defect (VSD), and left ventricular outflow tract obstruction (LVOTO) is debatable. This is our initial experience with pulmonary root translocation (PRT), a technique that aims to preserve the pulmonary valve function. METHODS: From July 2012 to October 2019, 16 patients underwent anatomical repair for TGA, VSD, and LVOTO. The median age was 12 months (range: 7 months to 13 years), and the median weight was 7.75 kg (range: 5.6-29.5 kg). Thirteen patients had a diagnosis of d-TGA and three had congenitally corrected transposition of the great arteries (cc-TGA). The surgical technique involved PRT from the left ventricle (LV) to the right ventricle and routing the LV to the aorta. The left ventricular outflow tract orifice resulting from the pulmonary root extraction was closed with a pericardial patch. In patients with cc-TGA, an atrial switch operation was added. A bidirectional Glenn was necessary in four patients with a long LV to aorta tunnel. One patient required a transannular patch to reconstruct the right ventricular outflow tract (RVOT). RESULTS: The median follow-up was 27 months. There was one hospital death due to residual mitral regurgitation. One patient died at home four months after hospital discharge. The remaining patients are doing well with adequate RVOT function and no valve regurgitation. CONCLUSIONS: Complete correction of TGA, VSD, and LVOTO using PRT was achieved with acceptable risk in patients with pliable and nondysplastic pulmonary valve. The translocated pulmonary root performed well in this short follow-up.
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Anomalías Múltiples , Procedimientos Quirúrgicos Cardíacos/métodos , Transposición Congénitamente Corregida de las Grandes Arterias/cirugía , Ventrículos Cardíacos/trasplante , Obstrucción del Flujo Ventricular Externo/cirugía , Adolescente , Niño , Preescolar , Femenino , Ventrículos Cardíacos/cirugía , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
We present a unique surgical complication in a 19-year-old patient who underwent a "supported" Ross procedure for congenital aortic stenosis. In the present case, herniation of pulmonary autograft material through coronary fenestrations in the Dacron supporting material can be appreciated. This case suggests a possible need to modify surgical technique to ensure that all autograft tissue remains contained within the Dacron bolster.
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Estenosis de la Válvula Aórtica/diagnóstico , Autoinjertos , Ventrículos Cardíacos/trasplante , Falla de Prótesis , Arteria Pulmonar/trasplante , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Procedimientos Quirúrgicos Cardiovasculares , Diagnóstico Diferencial , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Humanos , Angiografía por Resonancia Magnética , Masculino , Tereftalatos Polietilenos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/cirugía , Adulto JovenRESUMEN
Myocardial infarction (MI) is a primary cardiovascular disease threatening human health and quality of life worldwide. The development of engineered heart tissues (EHTs) as a transplantable artificial myocardium provides a promising therapy for MI. Since most MIs occur at the ventricle, engineering ventricular-specific myocardium is therefore more desirable for future applications. Here, by combining a new macroporous 3D iron oxide scaffold (IOS) with a fixed ratio of human pluripotent stem cell (hPSC)-derived ventricular-specific cardiomyocytes and human umbilical cord-derived mesenchymal stem cells, we constructed a new type of engineered human ventricular-specific heart tissue (EhVHT). The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Furthermore, when patched on the infarcted area, the EhVHT effectively promoted repair of heart tissues in vivo and facilitated the restoration of damaged heart function of rats with acute MI. Our results show that it is feasible to generate functional human ventricular heart tissue based on hPSC-derived ventricular myocytes for the treatment of ventricular-specific myocardium damage. STATEMENT OF SIGNIFICANCE: We successfully generated highly purified homogenous human ventricular myocytes and developed a method to generate human ventricular-specific heart tissue (EhVHT) based on three-dimensional iron oxide scaffolds. The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Patching the EhVHT on the infarct area significantly improved cardiac function in rat acute MI models. This EhVHT has a great potential to meet the specific requirements for ventricular damages in most MI cases and for screening drugs specifically targeting ventricular myocardium.
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Compuestos Férricos/farmacología , Ventrículos Cardíacos/crecimiento & desarrollo , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Animales , Diferenciación Celular/efectos de los fármacos , Fenómenos Electrofisiológicos , Pruebas de Función Cardíaca , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/trasplante , Ventrículos Cardíacos/ultraestructura , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Porosidad , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH. METHODS: The Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0. RESULTS: Twenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of - 14.12 (- 14.63, - 13.61), - 11.86 (- 12.35, - 11.36), - 17.33 (- 18.10, - 16.56), - 0.10 (- 0.10, - 0.09), 0.23 (0.21, 0.24), - 13.66 (- 15.71, - 11.62), and - 7.96 (- 7.99, - 7.93), respectively. CONCLUSIONS: SC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ).
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Hipertensión Arterial Pulmonar/terapia , Trasplante de Células Madre , Arteriolas/fisiopatología , Arteriolas/trasplante , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/trasplante , Hemodinámica , Humanos , Hipertensión Arterial Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/trasplanteRESUMEN
Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (-20 pA/pF at -140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.
Asunto(s)
Técnicas de Transferencia de Gen , Ventrículos Cardíacos/trasplante , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Proteínas Musculares/genética , Miocitos Cardíacos/trasplante , Canales de Potasio/genética , Células Madre/citología , Animales , Terapia Genética/métodos , Proteínas Fluorescentes Verdes/química , Ventrículos Cardíacos/patología , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/uso terapéutico , Proteínas Musculares/uso terapéutico , Técnicas de Placa-Clamp , Canales de Potasio/uso terapéutico , Ratas , Trasplante de Células MadreRESUMEN
The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.
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Contracción Miocárdica , Miocitos Cardíacos , Ingeniería de Tejidos , Vena Cava Superior , Animales , Células Cultivadas , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/trasplante , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/trasplante , Ratas , Ratas WistarRESUMEN
Mechanical circulatory assist devices are now commonly used in the treatment of severe heart failure as bridges to cardiac transplant, as destination therapy for patients who are not transplant candidates, and as bridges to recovery and "decision-making". These devices, which can be used to support the left or right ventricles or both, restore circulation to the tissues, thereby improving organ function. Left ventricular assist devices (LVADs) are the most common support devices. To care for patients with these devices, health care providers in emergency departments (EDs) and intensive care units (ICUs) need to understand the physiology of the devices, the vocabulary of mechanical support, the types of complications patients may have, diagnostic techniques, and decision-making regarding treatment. Patients with LVADs who come to the ED or are admitted to the ICU usually have nonspecific clinical symptoms, most commonly shortness of breath, hypotension, anemia, chest pain, syncope, hemoptysis, gastrointestinal bleeding, jaundice, fever, oliguria and hematuria, altered mental status, headache, seizure, and back pain. Other patients are seen for cardiac arrest, psychiatric issues, sequelae of noncardiac surgery, and trauma. Although most patients have LVADs, some may have biventricular support devices or total artificial hearts. Involving a team of cardiac surgeons, perfusion experts, and heart-failure physicians, as well as ED and ICU physicians and nurses, is critical for managing treatment for these patients and for successful outcomes. This review is designed for critical care providers who may be the first to see these patients in the ED or ICU.
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Insuficiencia Cardíaca/terapia , Corazón Auxiliar/efectos adversos , Corazón Auxiliar/normas , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/etiología , Taponamiento Cardíaco/complicaciones , Taponamiento Cardíaco/etiología , Toma de Decisiones , Diagnóstico Diferencial , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/trasplante , Hemodinámica/fisiología , Hemólisis/fisiología , Humanos , Unidades de Cuidados Intensivos/organización & administración , Neumotórax/complicaciones , Neumotórax/etiología , Trombosis/complicaciones , Trombosis/etiología , Trasplante/instrumentación , Trasplante/métodos , Resultado del TratamientoAsunto(s)
Fibrilación Atrial/cirugía , Trasplante de Médula Ósea/métodos , Ventrículos Cardíacos/trasplante , Trasplante de Células Madre Hematopoyéticas/métodos , Imagenología Tridimensional , Anciano , Fibrilación Atrial/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging hearts. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations. Monocultured NRVCs displayed the senescence-associated phenotypes, characterized by an increase in the number of ß-galactosidase-positive cells and decreases in the degradation and disappearance of cellular organelles in a time-dependent manner. The levels of reactive oxygen species and malondialdehyde were elevated, whereas the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased, along with upregulation of p53, p21(Cip1/Waf1), and p16(INK4a) in the aging cardiomyocytes. These deleterious alterations were abrogated in aging NRVCs cocultured with BMSCs. Qualitatively, the same senescent phenotypes were consistently observed in aging rat hearts. Notably, BMSC transplantation significantly prevented these detrimental alterations and improved the impaired cardiac function in the aging rats. In summary, BMSCs possess strong antisenescence action on the aging NRVCs and hearts and can improve cardiac function after transplantation in aging rats. The present study, therefore, provides an alternative approach for the treatment of heart failure in the elderly population.
Asunto(s)
Diferenciación Celular , Senescencia Celular , Insuficiencia Cardíaca/terapia , Trasplante de Células Madre Mesenquimatosas , Miocitos Cardíacos/trasplante , Animales , Células de la Médula Ósea/citología , Insuficiencia Cardíaca/patología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/trasplante , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/terapia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , RatasRESUMEN
Clinical echocardiographic assessment of left ventricular (LV) systolic and diastolic function is routinely performed following orthotopic heart transplantation (OHT). The purpose of this study was to determine whether echocardiographic indices of LV diastolic function correlate with pulmonary capillary wedge pressure (PCWP) in the transplanted heart. Patients who had OHT between June 2009 and November 2011 underwent transthoracic echocardiography and right heart catheterization (RHC) at approximately 1 year post transplantation. We retrospectively assessed 33 potential parameters of LV diastolic function using 2-dimensional, spectral Doppler and tissue Doppler echocardiography. We measured PCWP by RHC. We compared echocardiographic measures with PCWP using linear regression analysis. Ninety-five patients (mean age 49 ± 13 years, 73 males, mean LV ejection fraction 62 ± 10%) were included in the study. Overall, echocardiographic parameters of LV diastolic function demonstrated poor correlation with PCWP. By linear regression, the parameter that most strongly correlated with PCWP was left atrial (LA) minimum area in the apical 4-chamber view (p = 0.002, r(2) = 0.1). Comparing patients with PCWP ≤ 12 mmHg and those with PCWP > 12 mmHg, the parameter that demonstrated the most significant difference was LA minimum area in the apical 2-chamber view (p = 0.002), and comparing patients with PCWP ≤ 15 mmHg and those with PCWP > 15 mmHg, the most significant difference was peak early diastolic velocity of the mitral annulus (p = 0.02). In patients with cardiac allografts, clinical echocardiographic measures of LV diastolic function correlate poorly with PCWP.
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Cateterismo de Swan-Ganz , Diástole , Ecocardiografía Doppler , Rechazo de Injerto/diagnóstico , Trasplante de Corazón/efectos adversos , Ventrículos Cardíacos/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Presión Esfenoidal Pulmonar , Disfunción Ventricular Izquierda/diagnóstico , Función Ventricular Izquierda , Adulto , Aloinjertos , Biopsia , Femenino , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/etiología , Rechazo de Injerto/fisiopatología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/trasplante , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Cell therapies offer the potential to improve cardiac function after myocardial infarction. Although injection of single-cell suspensions has proven safe, cell retention and survival rates are low. Tissue-engineered grafts allow cell delivery with minimal initial cell loss and mechanical support to the heart. However, graft performance cannot be easily compared, and optimal construct thickness, vascularization, and survival kinetics are unknown. METHODS AND RESULTS: Cardiac tissue slices (CTS) were generated by sectioning mouse hearts (n=40) expressing firefly luciferase and green fluorescent protein into slices of defined size and thickness using a vibrating blade microtome. Bioluminescence imaging of CTS transplanted onto hearts of immunodeficient mice demonstrated survival of ≤30% of transplanted cells. Cardiac slice perfusion was re-established within 3 days, likely through anastomosis of pre-existing vessels with the host vasculature and invasion of vessels from the host. Immunofluorescence showed a peak in cell death 3 days after transplantation and a gradual decline thereafter. MRI revealed preservation of contractile function and an improved ejection fraction 1 month after transplantation of CTS (28±2% CTS versus 22±2% control; P=0.05). Importantly, this effect was specific to CTS because transplantation of skeletal muscle tissue slices led to faster dilative remodeling and higher animal mortality. CONCLUSIONS: In summary, this is the first study to use CTS as a benchmark to validate and model tissue-engineered graft studies. CTS transplantation improved cell survival, established reperfusion, and enhanced cardiac function after myocardial infarction. These findings also confirm that dilative remodeling can be attenuated by topical transplantation of CTS but not skeletal muscle tissue grafts.
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Células Madre Embrionarias/trasplante , Ventrículos Cardíacos/trasplante , Infarto del Miocardio/cirugía , Ingeniería de Tejidos , Trasplante de Tejidos/métodos , Animales , Animales Recién Nacidos , Femenino , Genes Reporteros , Supervivencia de Injerto , Proteínas Fluorescentes Verdes/genética , Humanos , Luciferasas de Luciérnaga/genética , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Modelos Animales , Contracción Miocárdica , Tamaño de los Órganos , Músculo Cuádriceps , Distribución AleatoriaAsunto(s)
Aneurisma/cirugía , Ventrículos Cardíacos/trasplante , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón , Arteria Pulmonar/trasplante , Obstrucción del Flujo Ventricular Externo/cirugía , Aneurisma/complicaciones , Aneurisma/diagnóstico , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Estenosis de la Válvula Pulmonar/complicaciones , Estenosis de la Válvula Pulmonar/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Obstrucción del Flujo Ventricular Externo/complicacionesRESUMEN
Tissue engineering and stem cell transplantation are promising novel therapies for myocardial repair. A major barrier to cell survival after transplantation involves inadequate vascularization. Continuous observation of cardiac tissue engraftment and angiogenesis could help understand these processes and allow for identification of the optimal conditions for these therapeutic interventions. We investigated the ability of a skin-fold chamber model to allow for engraftment of differentiated myocardial tissue in mice. Neonatal atrial and ventricular tissues were implanted in the in vivo chambers. All myocardial implants had a high rate of engraftment (86-95%). Tissue engraftment was preceded by a 'bleeding phase' in both the atrial and ventricular implants. This occurred earlier in ventricular compared with atrial implants. Spontaneous contractions were observed after an average of 13 days after implantation in all chambers but occurred earlier in ventricular compared with atrial implants. The host cells surrounded the myocardial implants circumferentially, but have limited infiltration into these grafts. This is the first report of successful ectopic engraftment of differentiated myocardium using a skin-fold chamber. This model is invaluable for real-time observation of early angiogenesis and tissue growth during in vivo myocardial engineering and myocardial regeneration.
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Supervivencia de Injerto , Trasplante de Corazón , Microscopía Fluorescente , Microscopía por Video , Neovascularización Fisiológica , Regeneración , Animales , Animales Recién Nacidos , Procedimientos Quirúrgicos Dermatologicos , Proteínas Fluorescentes Verdes/biosíntesis , Proteínas Fluorescentes Verdes/genética , Atrios Cardíacos/metabolismo , Atrios Cardíacos/trasplante , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/trasplante , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Contracción Miocárdica , Factores de TiempoRESUMEN
Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy.
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Ventrículos Cardíacos/trasplante , Miocardio/metabolismo , Miocitos Cardíacos/citología , Células Madre/citología , Ingeniería de Tejidos/métodos , Anciano , Anciano de 80 o más Años , Animales , Diferenciación Celular , Movimiento Celular , Técnicas de Cocultivo , Femenino , Perfilación de la Expresión Génica , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Miocardio/citología , Miocitos Cardíacos/fisiología , Miocitos Cardíacos/trasplante , Fenotipo , Trasplante de Tejidos/métodosRESUMEN
Congenital abnormalities of the tricuspid valve without downward displacement of the septal and posterior tricuspid leaflets are uncommon causes of tricuspid regurgitation. Progressive tricuspid regurgitation can lead to right heart dilatation, arrhythmia, and irreversible deterioration of right ventricular function. Tricuspid valve repair is an important method to stabilize symptomatic children because tricuspid valve replacement has a poor prognosis. We report the successful use of right ventricular trabecula as a "neopapillary muscle" for treating severe low-pressure tricuspid regurgitation in children.
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Ventrículos Cardíacos/trasplante , Insuficiencia de la Válvula Tricúspide/cirugía , Válvula Tricúspide/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Preescolar , Humanos , MasculinoRESUMEN
PURPOSE: The arrhythmogenic effect of stem cells transplantation (SCT) in an infarct myocardium is still unknown. We investigated arrhythmogenicity of SCT in rat cryo-infarct model. MATERIALS AND METHODS: In rat cryo-infarct model, bone marrow mononuclear stem cells (MNSC, 1 x 10(7) cells) were transplanted into the infarct border zone (BZ) of the LV epicardium. We compared the optical mapping and inducibility of ventricular tachycardia/fibrillation (VT/VF) among normal (n=5), cryo-infarct (n=6), and SCT rats (n=6). RESULTS: The VT/VF inducibility was higher in the cryo- infarct (47.2%, p=0.001) and SCT groups (34.6%, p=0.01) than in the normal group (12.8%). The induced VT/VF episodes persisted for more than 2 minutes in 4.3%, 26.4% and 17.3% in the normal, cryo-infarct and SCT group, respectively. In the SCT group, the action potential duration at 70% was shorter at the SCT site than the BZ during SR (75.2 +/- 8.1 vs. 145.6 +/- 4.4 ms, p=0.001) and VT (78.2 +/- 13.0 vs. 125.7 +/- 21.0 ms, p= 0.001). Conduction block was observed at the SCT site and BZ during VT. However, no reentry or ectopic foci were observed around the SCT sites. CONCLUSION: The electrical conduction was improved by SCT without evidence of augmentation of arrhythmia in the rat cryo-infarct model.
Asunto(s)
Arritmias Cardíacas/etiología , Trasplante de Médula Ósea/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infarto del Miocardio/cirugía , Potenciales de Acción , Animales , Modelos Animales de Enfermedad , Conductividad Eléctrica , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/trasplante , Técnicas In Vitro , Infarto del Miocardio/patología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Engineered heart tissue (EHT) can be generated from cardiomyocytes and extracellular matrix proteins and used to repair local heart muscle defects in vivo. Here, we hypothesized that pouch-like heart muscle constructs can be generated by using a novel EHT-casting technology and applied as heart-embracing cardiac grafts in vivo. METHODS AND RESULTS: Pouch-like EHTs (inner/outer diameter: 10/12 mm) can be generated mainly from neonatal rat heart cells, collagen type I, and serum containing culture medium. They contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. First implantation studies indicate that pouch-like EHTs can be slipped over uninjured adult rat hearts to completely cover the left and right ventricles. Fourteen days after implantation, EHT-grafts stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived. CONCLUSIONS: Pouch-like EHTs can be generated with structural and functional properties of native myocardium. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo.
Asunto(s)
Órganos Bioartificiales , Trasplante de Corazón/métodos , Ingeniería de Tejidos/métodos , Animales , Animales Recién Nacidos , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/crecimiento & desarrollo , Ventrículos Cardíacos/trasplante , Corazón Auxiliar/parasitología , Contracción Miocárdica/fisiología , Miocitos Cardíacos/trasplante , Técnicas de Cultivo de Órganos/métodos , Pericardio/citología , Pericardio/crecimiento & desarrollo , Ratas , Ratas WistarRESUMEN
PURPOSE: Homograft benefits include excellent hemodynamics, resistance to infection, decreased thromboembolic events, ease of handling, and lack of need for anticoagulation. We examined the short and mid-term results of right ventricular outflow tract (RVOT) reconstruction using cryopreserved homografts. PATIENTS AND METHODS: From May 1998 to May 2005, 20 patients (male:female=10:10) underwent RVOT reconstruction using cryopreserved homografts. The median age was 23.8 years (range, 0.9 to 43.3 years) and the median body weight was 57 kg (range, 7.3 to 80 kg). Eighteen patients underwent re-operation after shunt or corrective operations. Homograft failure was defined as either re-operation for homograft replacement or patient death. Homograft dysfunction was defined as grade 3 or more than 3 of graft regurgitation and more than 40 mmHg of transvalvular pressure gradient under echocardiographic examination. RESULTS: No operative mortality occurred and there were three major complications. Graft failure was observed in one male patient with tetralogy of Fallot. The 8-year freedom from graft failure was 87.5+/-11.7% and the 7-year freedom from graft dysfunction was 62.3+/-17.9%. Multivariable analysis revealed that the independent factor for graft dysfunction was age less than 10 years. In the analysis according to age group, the 7-year freedom from graft dysfunction in the group of patients older than 10 years was 100% and 25.0+/-21.7% in patients age 10 or younger (p= 0.03). CONCLUSION: Right ventricular outflow reconstruction using cryopreserved homografts provided excellent short and mid-term results in most patients in this study. However, in patients younger than 10 years old, homografts for RVOT reconstruction showed a high dysfunction rate at mid-term.
Asunto(s)
Cardiopatías/cirugía , Ventrículos Cardíacos/trasplante , Adolescente , Adulto , Niño , Preescolar , Criopreservación , Femenino , Humanos , Lactante , Complicaciones Intraoperatorias , Masculino , Complicaciones Posoperatorias , Trasplante Homólogo/efectos adversos , Resultado del TratamientoRESUMEN
Para evaluar la efectividad del transplante de células madre en pacientes con infarto del miocardio e insuficiencia cardíaca crónica severa mediante técnicas de cardiología nuclear, se estudiaron 15 pacientes revascularizados: nueve (grupo I) recibieron células madre autólogas de médula ósea. Los 6 restantes correspondieron al grupo II (controles). Se les realizó evaluación clínica, ventriculografía radioisotópica y gammagrafía de perfusión con SPECT-gatillado (tecnecio-99m MIBI; protocolo de dos días: dipiridamol reposo), antes y tres meses después del proceder. A los tres meses hubo mejoría clínica en el 89 por ciento de los pacientes del grupo I. La fracción de eyección de ventrículo izquierdo aumentó: de 32±9 por ciento a 44±13 por ciento (p=0.03; grupo I) y de 38±2 por ciento a 48±14 por ciento (p NS; grupo II). La velocidad máxima de llenado se incrementó de 120±11 a 196±45 VTD/seg (p=0.03; grupo I). El score sumado del dipiridamol disminuyó significativamente sólo en el grupo I (de 35±5 a 23±14; p=0.02). La mejoría de la perfusión estuvo relacionada con el sitio de implante en el 60 por ciento de los casos. Concluimos que el transplante de células madre de médula ósea es efectivo en pacientes con insuficiencia cardíaca crónica severa de etiología isquémica.