9 research outputs found
Intrapericardial delivery of apa-microcapsules as promising stem cell therapy carriers in an experimental acute myocardial infarction model
The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-L-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre-and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment
The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca-10(PO4)(5.6)(SRO4)(0.4)(OH)(1.6) following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone.MINECO (MAT2015-64831-R, MAT2016-75611-R AEI/FEDER, UE y BI02015-66266-R)
Institute de Salud Carlos III (RD12-0019-0032)
European Research Council (Advanced Grant VERDI; ERC-2015-AdG Proposal 694160
Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep.
Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and forested osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis
Histopathologic features of the vagus nerve after electrical stimulation in swine
This paper describes the histological features
of the vagus nerve after its stimulation with an
electrostimulation system that is being developed for
morbid obesity treatment.
An electrostimulation system was implanted
laparoscopically around the ventral vagal trunk of five
Large White female pigs (49.63±1.94kg.). Vagal nerve
stimulation was performed by continuous constant
voltage current pulses. Thoracic samples of both ventral
and dorsal vagal trunks were obtained thoracoscopically
one month after implantation. Animals were sacrificed
one month after thoracoscopic vaguectomy. Tissue
samples were then harvested from the vagal nerve at the
implantation site, 1cm cranial to it, thoracic portion of
ventral and dorsal vagal trunks, sub-diaphragmatic
dorsal vagal trunk, left and right vagus nerves.
Specimens were analysed with light microscope. The
severity of the lesions was graded from 0 to 4 (0: no
lesion, 1: mild, 2: moderate, 3: severe and 4: extremely
severe), taking into account fibrosis, vascularization,
necrosis, fiber degeneration and inflammation.
Electrode implantation resulted in thickened
epineurium and endoneural connective tissue. The
greatest lesion score was evidenced at the leads
implantation site in the ventral vagal trunk, followed by,
in order of decreasing lesion severity, left vagus nerve,
thoracic portion of ventral vagal trunk, subdiaphragmatic
dorsal vagal trunk, thoracic portion of dorsal vagal trunk
and right vagus nerve.
The stimulation device used in this study caused
connective tissue growth, greatest in the samples located
closer to the implantation site. However, there was no
sign of altered vascularization in any studied specimen
Empleo del modelo animal en la formación en endoscopia diagnóstica y terapéutica de la vía biliar
Objetivo. Mostrar nuestra experiencia en la formación en endoscopia terapéutica de la vía biliar en modelo animal. Materiales y métodos. Esta actividad formativa tiene una duración de 13 horas y comienza iniciando al alumno en las diferencias anatómicas de las especies que se emplean, la porcina y la canina, con respecto a la anatomía humana. Las prácticas consisten en habituar al endoscopista a la visión lateral del duodenoscopio; se realizan en un modelo porcino debido a que es más sencillo atravesar el esfínter pilórico, aunque no suele ser muy adecuado para la canulación de la papila duodenal. Tras superar la primera fase se utiliza el modelo canino, que permite adquirir las habilidades y destrezas propias de esta técnica. La evaluación de los resultados se realiza mediante una encuesta anónima. Resultados. El 76% de los alumnos confirma que ha avanzado mucho con este entrenamiento, un 18% regular y un 6% poco. El 75% considera que, tras realizar esta actividad de formación, se encontraría capacitado para llevar a cabo la técnica en su hospital. El 94% de los alumnos recomendaría esta actividad a sus compañeros. Conclusiones. El empleo del modelo animal en la formación en colangiopancreatografía retrógada endoscópica (CPRE) permite la adquisición de habilidades básicas necesarias para la práctica, ya que posibilita la repetición de las maniobras y la tutela continuada. Consideramos que con esta metodología mixta se podría acortar la curva de aprendizaje de la CPRE y disminuiría la iatrogenia en las primeras fases
CIBER-CLAP (CIBERCV Cardioprotection Large Animal Platform): A multicenter preclinical network for testing reproducibility in cardiovascular interventions
Despite many cardioprotective interventions have shown to protect the heart against ischemia/reperfusion injury in the experimental setting, only few of them have succeeded in translating their findings into positive proof-of-concept clinical trials. Controversial and inconsistent experimental and clinical evidence supports the urgency of a disruptive paradigm shift for testing cardioprotective therapies. There is a need to evaluate experimental reproducibility before stepping into the clinical arena. The CIBERCV (acronym for Spanish network-center for cardiovascular biomedical research) has set up the “Cardioprotection Large Animal Platform” (CIBER-CLAP) to perform experimental studies testing the efficacy and reproducibility of promising cardioprotective interventions based on a pre-specified design and protocols, randomization, blinding assessment and other robust methodological features. Our first randomized, control-group, open-label blinded endpoint experimental trial assessing local ischemic preconditioning (IPC) in a pig model of acute myocardial infarction (n = 87) will be carried out in three separate sets of experiments performed in parallel by three laboratories. Each set aims to assess: (A) CMR-based outcomes; (B) histopathological-based outcomes; and (C) protein-based outcomes. Three core labs will assess outcomes in a blinded fashion (CMR imaging, histopathology and proteomics) and 2 methodological core labs will conduct the randomization and statistical analysis.Groups part of the CIBERCV receive competitive structural funding from the Insituto de Salud Carlos III (ISCiii) through the Ministry of Science, Innovation and Universities (MICINN). X.R. has received support from the SEC-CNIC CARDIOJOVEN fellowship program.Peer reviewe
CIBER-CLAP (CIBERCV Cardioprotection Large Animal Platform) : A multicenter preclinical network for testing reproducibility in cardiovascular interventions
Altres ajuts: Groups part of the CIBERCV receive competitive structural funding from the Insituto de Salud Carlos III (ISCiii) through the Ministry of Science, Innovation and Universities (MICINN). X.R. has received support from the SEC-CNIC CARDIOJOVEN fellowship program.Despite many cardioprotective interventions have shown to protect the heart against ischemia/reperfusion injury in the experimental setting, only few of them have succeeded in translating their findings into positive proof-of-concept clinical trials. Controversial and inconsistent experimental and clinical evidence supports the urgency of a disruptive paradigm shift for testing cardioprotective therapies. There is a need to evaluate experimental reproducibility before stepping into the clinical arena. The CIBERCV (acronym for Spanish network-center for cardiovascular biomedical research) has set up the "Cardioprotection Large Animal Platform" (CIBER-CLAP) to perform experimental studies testing the efficacy and reproducibility of promising cardioprotective interventions based on a pre-specified design and protocols, randomization, blinding assessment and other robust methodological features. Our first randomized, control-group, open-label blinded endpoint experimental trial assessing local ischemic preconditioning (IPC) in a pig model of acute myocardial infarction (n = 87) will be carried out in three separate sets of experiments performed in parallel by three laboratories. Each set aims to assess: (A) CMR-based outcomes; (B) histopathological-based outcomes; and (C) protein-based outcomes. Three core labs will assess outcomes in a blinded fashion (CMR imaging, histopathology and proteomics) and 2 methodological core labs will conduct the randomization and statistical analysis