Papers by Natalia Lausada
OncoImmunology, Oct 19, 2023
Introducción Este programa de pasantías está destinado a alumnos que cursan el último año en Escu... more Introducción Este programa de pasantías está destinado a alumnos que cursan el último año en Escuelas públicas de enseñanza Secundaria, especialmente dirigido a colegios de menor acceso al ambiente académico. Los pasantes son guiados en la ejecución de un proyecto de investigación demostrativo de las etapas del método científico, lo que comprende el planteamiento de una hipótesis de trabajo, la búsqueda bibliográfica, el diseño de la estrategia o protocolo experimental, el desempeño técnico en la obtención de datos, su observación, análisis y discusión crítica para converger en una conclusión de elaboración personal.
vol. 2, no. 1, 2010
mirage Afectación de vías de apoptosis cuando se administra inmunosupresión a los donantes: rol d... more mirage Afectación de vías de apoptosis cuando se administra inmunosupresión a los donantes: rol de TNFA, BAX y BCL-2. SeDiCI. Iniciar sesión. ...
Transplant International, Jan 12, 2023
There is an urgent need to address the shortage of potential multivisceral grafts in order to red... more There is an urgent need to address the shortage of potential multivisceral grafts in order to reduce the average time in waiting list. Since donation after circulatory death (DCD) has been successfully employed for other solid organs, a thorough evaluation of the use of intestinal grafts from DCD is warranted. Here, we have generated a model of Maastricht III DCD in rodents, focusing on the viability of intestinal and multivisceral grafts at five (DCD5) and twenty (DCD20) minutes of cardiac arrest compared to living and brain death donors. DCD groups exhibited time-dependent damage. DCD20 generated substantial intestinal mucosal injury and decreased number of Goblet cells whereas grafts from DCD5 closely resemble those of brain death and living donors groups in terms intestinal morphology, expression of tight junction proteins and number of Paneth and Globet cells. Upon transplantation, intestines from DCD5 showed increased ischemia/reperfusion damage compared to living donor grafts, however mucosal integrity was recovered 48 h after transplantation. No differences in terms of graft rejection, gene expression and absorptive function between DCD5 and living donor were observed at 7 post-transplant days. Collectively, our results highlight DCD as a possible strategy to increase multivisceral donation and transplantation procedures.
Todo trasplante de órganos requiere de un donante, el cual, según el caso, puede ser vivo o falle... more Todo trasplante de órganos requiere de un donante, el cual, según el caso, puede ser vivo o fallecido. Pese a que los mejores resultados se observan cuando el órgano proviene de un donante vivo, el mayor porcentaje de órganos destinados a trasplante se obtienen de donantes con criterios neurológicos de muerte encefálica. La muerte cerebral induce un aumento de la permeabilidad de membranas a nivel intestinal, produciendo una traslocación bacteriana, que conlleva a una producción de citoquinas pro-inflamatorias, generando éstas a su vez la auto-perpetuidad y amplificación del proceso inflamatorio e induciendo además el daño de órganos remotos. El trasplante de intestino con donante vivo una práctica casi nula mundialmente, por lo cual la enorme mayoría de los procedimientos se realizan con órganos procurados de donantes en muerte encefálica. Por tal motivo, el estudio de la fisiopatología de este proceso y la búsqueda de estrategias para mejorar la viabilidad de los órganos represent...
The FASEB Journal, Apr 1, 2016
Limited autologous vascular graft availability and poor patency rates of synthetic grafts for byp... more Limited autologous vascular graft availability and poor patency rates of synthetic grafts for bypass or replacement of small-diameter arteries remain a concern in the surgical community. These limitations could potentially be improved by a tissue engineering approach. We report here our progress in the development and in vivo testing of a stem-cell-based tissue-engineered vascular graft for arterial applications. Poly(ester urethane)urea scaffolds (length ¼ 10 mm; inner diameter ¼ 1.2 mm) were created by thermally induced phase separation (TIPS). Compound scaffolds were generated by reinforcing TIPS scaffolds with an outer electrospun layer of the same biomaterial (ES-TIPS). Both TIPS and ES-TIPS scaffolds were bulk-seeded with 10Â10 6 allogeneic, LacZ-transfected, muscle-derived stem cells (MDSCs), and then placed in spinner flask culture for 48 h. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks. Angiograms and histological assessment were performed at the time of explant. Cell-seeded constructs showed a higher patency rate than the unseeded controls: 65% (ES-TIPS) and 53% (TIPS) versus 10% (acellular TIPS). TIPS scaffolds had a 50% mechanical failure rate with aneurysmal formation, whereas no dilation was observed in the hybrid scaffolds. A smooth-muscle-like layer of cells was observed near the luminal surface of the constructs that stained positive for smooth muscle a-actin and calponin. LacZþ cells were shown to be engrafted in the remodeled construct. A confluent layer of von Willebrand Factor-positive cells was observed in the lumen of MDSC-seeded constructs, whereas acellular controls showed platelet and fibrin deposition. This is the first evidence that MDSCs improve patency and contribute to the remodeling of a tissue-engineered vascular graft for arterial applications.
Acta Bioquimica Clinica Latinoamericana, Jun 1, 2018
En base a la gran cantidad de grupos de trabajo que utilizan animales de laboratorio dentro del á... more En base a la gran cantidad de grupos de trabajo que utilizan animales de laboratorio dentro del ámbito de la Facultad, y teniendo en cuenta la necesidad de realizar un buen control del uso y cuidado de los mismos, en Julio de 2012 se crea el CICUAL de la Fac. de Cs. Médicas (CICUAL-FCM) mediante Resolución 230/12 del HCD. Depende de la Secretaría de Ciencia y Técnica de la FCM y entre sus integrantes se incluyen Médicos Veterinarios, Investigadores con experiencia en experimentación con animales y Personal de la Comisión de Bioterio de la Facultad. Tiene por objetivos: Revisar, aprobar y registrar los protocolos de uso experimental y cuidado de los animales de laboratorio; supervisar el cumplimiento de las normativas para el cuidado y uso de animales de laboratorio, asesorar a los investigadores y docentes sobre los principios 3R (refinamiento, reducción y reemplazo), capacitar al personal e informar lo actuado. Durante sus dos primeras reuniones en 2012, se aprueba el Manual de Fun...
Introducción La falla multiorgánica es una de las causas de morbi-mortalidad en pacientes con tra... more Introducción La falla multiorgánica es una de las causas de morbi-mortalidad en pacientes con trasplante intestinal. La lesión por isquemia-reperfusión intestinal (IRI) provoca ruptura de la barrera del intestino con impacto en órganos distantes, ya sea por sepsis, traslocación bacteriana o por activar una respuesta inflamatoria sistémica Objetivos: evaluar la respuesta histológica del tejido intestinal, pulmonar y hepático luego de un período de 35 minutos de isquemia intestinal por clampeo de la arteria mesentérica superior (AMS) seguidos de 60 minutos de reperfusión.
Resumen El trasplante de intestino (TXI) constituye una opción terapéutica para pacientes con ins... more Resumen El trasplante de intestino (TXI) constituye una opción terapéutica para pacientes con insuficiencia intestinal que se ven imposibilitados de continuar bajo nutrición parenteral total. La injuria por isquemia-reperfusión es una complicación inherente al TXI capaz de comprometer la funcionalidad y la supervivencia del injerto y del paciente. Por tal motivo, diversas estrategias, aún en etapas experimentales, son propuestas para atenuar este daño, sin existir un consenso sobre cual es la más apropiada. El precondicionamiento isquémico (PCI) consiste en exponer a un órgano a períodos breves de isquemia seguidos de reperfusión previamente a una fase de isquemia prolongada. Inicialmente descripto para atenuar la IIR en miocardio, el PCI aparece como una alternativa promisoria para ser utilizada nivel intestinal. El objetivo de este trabajo es evaluar si el PCI atenúa el daño ocasionado por la isquemia fría y la reperfusión en un modelo experimental de TXI. Se utilizaron 24 ratas W...
Journal of Trauma and Acute Care Surgery, 2021
BACKGROUND The hemodynamic maintenance of brain-dead donors will influence the quality of the org... more BACKGROUND The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01). CONCLUSION Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.
Transplantation Proceedings, 2016
Background. Intestinal ischemia-reperfusion injury occurs after different surgical treatments, in... more Background. Intestinal ischemia-reperfusion injury occurs after different surgical treatments, including intestinal transplantation. This harmful process may have an effect in remote organs, leading to multiple organ dysfunction syndrome and death. Therefore, to establish strategies to attenuate local and remote damage constitutes a challenge for experimental and clinical surgeons in the intestinal surgical field. Methods. We evaluated the effect of ischemic preconditioning and tacrolimus pretreatment applied alone and in combination against local and remote damage caused by prolonged intestinal ischemia-reperfusion injury in a mouse model of warm ischemia. Results. Ischemic preconditioning applied alone and in combination with tacrolimus decreased histological damage (P < .05), number of apoptotic cells (P < .05), nitrosative stress (P < .01), and serum lactate dehydrogenase activity (P < .05) and lowered uremia (P < .05) compared with untreated post-reperfused intestines. Regarding remote organ damage, combination therapy was the unique condition able to attenuate lung (mainly neutrophil infiltration and hemorrhage), liver (sinusoidal congestion and hepatic vacuolization), and kidney (acute tubular necrosis and hydropic degeneration) histological alterations (P < .05), compared with the untreated group. Conclusions. These results support the application of these strategies in combination to minimize the impact of ischemia-reperfusion injury in the whole organism as a strategy to prevent multiple organ dysfunction syndromes and minimize the clinical impact.
Transplantation Journal, 2010
A pig model with a deep large burn was used to study the regeneration process induced by mesenchy... more A pig model with a deep large burn was used to study the regeneration process induced by mesenchymal stem cells (MSCs) and acellular pig dermal matrices, made intelligent by the combination with biodegradable nanofibers loaded with growth factors (granulocitemacrophage colony-stimulating factor and epidermal growth factor) and coated with the anti-CD44 monoclonal antibody (intelligent acellular dermal matrices, IADMs). These IADMs are specially designed to integrate in the wound bed as new biological scaffolds as well as to specifically recruit and attach circulating and/or externally applied MSCs through the anti-CD44 antibody while delivering precise amounts of growth factors. In this way, the reparative process as well as the aesthetic and functional results were enhanced in our burn model. The animal survived, the wound was completely closed, and total regeneration of the skin was obtained without much scarring. Surprisingly, hair follicles and other skin appendages developed despite the severity and deepness of the burn. Even burned muscles and ribs seemed to have undergone a regenerative process by the end of the study. Based on these findings, we have proposed the use of IADMs and autologous, allogeneic or xenogeneic MSCs, as a new paradigm for the future treatment of large burns and probably other dermatological and cosmetic human conditions.
Resumen La microcirugía complementa diversas especialidades quirúrgicas a fin de magnificar la es... more Resumen La microcirugía complementa diversas especialidades quirúrgicas a fin de magnificar la estructura a intervenir; y en profesiones no-médicas se utiliza para realizar técnicas altamente complejas en roedores de laboratorio. La enseñanza de la técnica se realiza con ejercicios de complejidad creciente hasta culminar realizando con éxito anastomosis vasculares y nerviosas en estructuras menores a los 2 mm. Estos ejercicios se llevan a cabo inicialmente en modelos inanimados y posteriormente en la rata de laboratorio. Nuestro objetivo es presentar la metodología pedagógica y los resultados obtenidos en 13 años de experiencia de enseñanza de la técnica microquirúrgica en nuestra facultad. Anualmente se dictan cursos desde el año 2000 hasta la fecha. En cada curso, en una primer etapa se dictan conceptos teóricos generales de la técnica, manejo quirúrgico de la rata de laboratorio y su anatomía en abordajes vasculares femorales, carotídeos y abdominales. Posteriormente se realizan ...
Uploads
Papers by Natalia Lausada