José A. García de Jalón

Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical Swine model of myocardial infarction.

The aim of the study was to determine the long-term effect of transplantation of adipose-derived stromal cells (ADSCs) in a preclinical model of ischemia/reperfusion (I/R). I/R was induced in 28 Goettingen minipigs by 120 min of coronary artery occlusion followed by reperfusion. Nine days later, surviving animals were allocated to receive transendocardial injection of a mean of 213.6 ± 41.78 million green fluorescent protein (GFP)-expressing ADSCs (n = 7) or culture medium as control (n = 9). Heart function, cell engraftment, and histological analysis were performed 3 months after transplantation. Transplantation of ADSCs induced a statistically significant long-lasting (3 months) improvement in cardiac function and geometry in comparison with control animals. Functional improvement was associated with an increase in angiogenesis and vasculogenesis and a positive effect on heart remodeling with a decrease in fibrosis and cardiac hypertrophy in animals treated with ADSCs. Despite the lack of cell engraftment after 3 months, ADSC transplantation induced changes in the ratio between MMP/TIMP. Our results indicate that transplantation of ADSCs, despite the lack of long-term significant cell engraftment, increases vessel density and prevents adverse remodeling in a clinically relevant model of myocardial infarction, strongly suggesting a paracrine-mediated effect. ADSCs thus constitute an attractive candidate for the treatment of myocardial infarction.

Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction

AIMS Although transplantation of skeletal myoblast (SkM) in models of chronic myocardial infarction (MI) induces an improvement in cardiac function, the limited engraftment remains a major limitation. We analyse in a pre-clinical model whether the sequential transplantation of autologous SkM by percutaneous delivery was associated with increased cell engraftment and functional benefit. METHODS AND RESULTS Chronically infarcted Goettingen minipigs (n = 20) were divided in four groups that received either media control or one, two, or three doses of SkM (mean of 329.6 x 10(6) cells per dose) at intervals of 6 weeks and were followed for a total of 7 months. At the time of sacrifice, cardiac function was significantly better in animals treated with SkM in comparison with the control group. A significantly greater increase in the DeltaLVEF was detected in animals that received three doses vs. a single dose of SkM. A correlation between the total number of transplanted cells and the improvement in LVEF and DeltaLVEF was found (P < 0.05). Skeletal myoblast transplant was associated with an increase in tissue vasculogenesis and decreased fibrosis (collagen vascular fraction) and these effects were greater in animals receiving three doses of cells. CONCLUSION Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.

Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility

We examine the impact of changes in microbiota induced by antibiotics on intestinal motility, gut inflammatory response, and the function and expression of toll-like receptors (TLRs). Alterations in mice intestinal microbiota were induced by antibiotics and evaluated by q-PCR and DGGE analysis. Macroscopic and microscopic assessments of the intestine were performed in control and antibiotic-treated mice. TLR expression was determined in the intestine by q-RT-PCR. Fecal parameter measurements, intestinal transit, and muscle contractility studies were performed to evaluate alterations in intestinal motility. Antibiotics reduced the total bacterial quantity 1000-fold, and diversity was highly affected by treatment. Mice with microbiota depletion had less Peyer’s patches, enlarged ceca, and mild gut inflammation. Treatment with antibiotics increased the expression of TLR4, TLR5, and TLR9 in the ileum and TLR3, TLR4, TLR6, TLR7, and TLR8 in the colon, and it reduced the expression of TLR2, TLR3, and TLR6 in the ileum and TLR2 and TLR9 in the colon. Antibiotics decreased fecal output, delayed the whole gut and colonic transit, and reduced the spontaneous contractions and the response to acetylcholine (ACh) in the ileum and colon. Activation of TLR4 by lipopolysaccharide (LPS) reverted the reduction of the spontaneous contractions induced by antibiotics in the ileum. Activation of TLR4 by LPS and TLR5 by flagellin reduced the response to ACh in the ileum in control mice. Our results confirm the role of the microbiota in the regulation of TLRs expression and shed light on the microbiota connection to motor intestinal alterations.

SQUAMOUS CELL CARCINOMA OF THE VAGINA AND CERVIX IN SHEEP - CASE REPORT

This report describes the clinical and histopathological characteristics of a squamous cell carcinoma infiltrating the cervix and the vaginal wall, producing reproductive symptoms and subnormal fertility in an adult ewe. Necropsy showed a large (15-cm-long) neoplastic mass infiltrating the vaginal wall and the cervix. Histopathological examination revealed atypical squamous epithelial cords invading the basal membrane and dermis, round anaplastic cells, focal areas of necrosis, keratinisation of isolated cells, and pronounced infiltration by mononuclear cells around the cords. No squamous cell carcinoma of such localisation has been reported from sheep before. In humans, this tumour is the most common gynaecological malignancy in the world.

Estudio experimental sobre quimioterapia focalizada en riñón mediante arpón magnético y administración intravenosa de nanopartículas ferrocarbonosas

El empleo de nanoparticulas en el transporte de farmacos es actualmente uno de los temas de interes prioritario dentro del campo de la investigacion biomedica. Nuestro objetivo es mostrar los resultados iniciales de un metodo inedito para focalizar en organos solidos nanoparticulas ferro carbonosas quimioportadoras. Hemos obtenido y caracterizado diversos tipos de nanoparticulas ferromagneticas, y hemos estudiado su comportamiento in vitro e in vivo en animales de experimentacion con dianas magneticas intrarrenales implantadas laparoscopicamente.