RESUMEN
Auricular chondrocytes, obtained from human auricular cartilage, can be grown easily in culture and have been used as a source for autologous cell/tissue transplant in several fields of reconstructive surgery. In addition, auricular chondrocytes/cartilage are being increasingly used for tissue engineering approaches to create artificial organs. Moreover, auricular chondrocytes have been used to improve biocompatibility of luminal surfaces of cardiovascular prostheses. This review looks at the progress in in vitro expansion of and differentiating strategies for auricular chondrocytes and compares the mechanical qualities of tissue-engineered cartilage from human auricular chondrocytes to those of native auricular cartilage. Finally, some of the most promising approaches for the in vivo application of auricular chondrocytes/cartilage will be briefly discussed.
Asunto(s)
Condrocitos/citología , Oído , Animales , Bovinos , Condrocitos/metabolismo , Humanos , Inmunohistoquímica , Ingeniería de TejidosRESUMEN
Auricular elastic cartilage is a potential source for lining of luminal surfaces of implantable vascular devices, such as stents and left ventricular assist devices with the purpose to improve their biocompatibility. Auricular chondrocytes are easily accessible, harvested, and isolated, and they have been shown to provide a strong adherent cell lining for left ventricular assist devices. Additionally, Dr. Rosenstrauch have shown that it is possible to genetically engineer auricular chondrocytes to produce antithrombogenic factors. Thus, implantable vascular devices, such as coronary stents covered with genetically engineered auricular chondrocytes might lower restenosis rates and provide a long-lasting biocompatible prosthesis. In this paper, to optimize the process of lining of artificial surfaces with auricular cartilage, we devise a mathematical model that describes the rate of cell division and growth of extracellular matrix as a function of the initial cell count, proximity to other cells, and the type of artificial surface. Our mathematical model was experimentally tested using two different cell cultures (auricular chondrocytes and dermal fibroblasts) seeded on different artificial surfaces (tc-treated polystyrene and aluminum foil). Excellent agreement between the model and experiment was obtained. This mathematical model can be used to, for example, determine the optimum number of initially seaded cells that would provide fastest coverage of a given artificial surface.
Asunto(s)
Condrocitos/citología , Condrocitos/fisiología , Condrogénesis/fisiología , Cartílago Auricular/citología , Cartílago Auricular/fisiología , Modelos Biológicos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Adhesión Celular , Agregación Celular , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Simulación por ComputadorRESUMEN
The focus of this work is on modeling blood flow in medium-to-large systemic arteries assuming cylindrical geometry, axially symmetric flow, and viscoelasticity of arterial walls. The aim was to develop a reduced model that would capture certain physical phenomena that have been neglected in the derivation of the standard axially symmetric one-dimensional models, while at the same time keeping the numerical simulations fast and simple, utilizing one-dimensional algorithms. The viscous Navier-Stokes equations were used to describe the flow and the linearly viscoelastic membrane equations to model the mechanical properties of arterial walls. Using asymptotic and homogenization theory, a novel closed, "one-and-a-half dimensional" model was obtained. In contrast with the standard one-dimensional model, the new model captures: (1) the viscous dissipation of the fluid, (2) the viscoelastic nature of the blood flow - vessel wall interaction, (3) the hysteresis loop in the viscoelastic arterial walls dynamics, and (4) two-dimensional flow effects to the leading-order accuracy. A numerical solver based on the 1D-Finite Element Method was developed and the numerical simulations were compared with the ultrasound imaging and Doppler flow loop measurements. Less than 3% of difference in the velocity and less than 1% of difference in the maximum diameter was detected, showing excellent agreement between the model and the experiment.
Asunto(s)
Algoritmos , Arterias/fisiología , Velocidad del Flujo Sanguíneo , Modelos Cardiovasculares , Animales , Elasticidad , Humanos , Ultrasonografía Doppler DúplexRESUMEN
The circadian temperature rhythm (CTR) profile holds promise for monitoring the domestic pig's responses to stress and illness. In the present study we quantified the CTR profile of nine growing-finishing swine using a time-series, small-group design. Temperature was monitored using a probe implanted in the ear for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed singly in pens. The dominant period of the temperature data was estimated with the autocorrelation function and then used in standard cosinor analysis to compute the amplitude (half of the distance between the highest and lowest value within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the cosine maximum). To examine the effect of procedural stress on CTR, we compared data from the first 3 days with those from subsequent days. Eight of the nine (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h, amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower (P = 0.03) during the first 3 days after instrumentation than during subsequent days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as reflected in attenuated CTR amplitude during the first 3 days after instrumentation; and 3) CTR adaptation to stress appears to occur over time.
Asunto(s)
Animales de Laboratorio , Temperatura Corporal/fisiología , Ritmo Circadiano/fisiología , Porcinos/fisiología , Adaptación Fisiológica , Animales , Femenino , Masculino , Monitoreo Ambulatorio/veterinaria , Estrés Psicológico/fisiopatologíaRESUMEN
As the prevalence and incidence of ischemic heart disease continue to increase, so does interest in ischemic heart failure management. Limitations of current therapies have led to research aimed at regenerating and repairing ischemically damaged myocardium through stem-cell therapy. Cell types being evaluated include embryonic stem cells, fetal and neonatal cardiomyocytes, skeletal myoblasts, bone marrow stem cells, peripheral blood CD34+ cells, endothelial progenitor cells, cardiac progenitor cells, and fibroblasts. Preclinical animal studies and promising early results of clinical trials now under way suggest that stem-cell therapy may soon become an important new tool in heart failure management.
Asunto(s)
Insuficiencia Cardíaca/cirugía , Isquemia Miocárdica/complicaciones , Trasplante de Células Madre/métodos , Insuficiencia Cardíaca/etiología , Humanos , Resultado del TratamientoRESUMEN
One possible way to expand the human heart donor pool is to include non-heart-beating human donors. To begin validating this approach, we developed an ex vivo cardiac perfusion circuit to support large mammalian hearts in Langendorff mode and beating-ejecting mode and to assess and improve their ischemic tolerance. In vivo hemodynamic data and heparinized blood (4.0 +/- 0.5 L) were collected from 6 anesthetized pigs. Hearts were isolated and connected to a recirculating perfusion circuit primed with autologous buffered blood (pH, 7.40). After retrograde aortic perfusion in Langendorff mode, the left atrium was gravity-filled at 10-20 mmHg, and the left ventricle began to eject against a compliance chamber in series with a systemic reservoir set to a hydraulic afterload of 100-120 mmHg. Left ventricular function was restored and maintained in all 6 hearts for 30 min. Cardiac output, myocardial oxygen consumption, stroke work, aortic pressure, left atrial pressure, and heart rate were measured. The mean myocardial oxygen consumption was 4.8 +/- 2.7 mL/min/100 g (95.8% of in vivo value); and mean stroke work, 5.3 +/- 1.1 g x m/100 g (58.95% of in vivo value). One resuscitated heart was exposed to 30 min of normothermic ischemic arrest, then flushed with Celsior and re-resuscitated. The ex vivo perfusion method described herein restored left ventricular ejection function and allowed assessment of ischemic tolerance in large mammalian hearts, potentially a 1st step toward including non-heart-beating human donors in the human donor pool.
Asunto(s)
Circulación Extracorporea , Resucitación , Animales , Gasto Cardíaco , Paro Cardíaco/fisiopatología , Paro Cardíaco/terapia , Hemodinámica , Técnicas In Vitro , Isquemia Miocárdica/fisiopatología , Consumo de Oxígeno , Volumen Sistólico , Porcinos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model. METHODS: In vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy. RESULTS: The efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining. CONCLUSIONS: Auricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.