Publications by authors named "Carlota Largo Aramburu"

4 Publications

  • Page 1 of 1

Graft infusion of adipose-derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study.

Clin Transplant 2021 04 5;35(4):e14226. Epub 2021 Feb 5.

TransplantChild ERN, Idipaz Institute, La Paz University Hospital, Madrid, Spain.

Background: Mesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose-derived MSC (Ad-MSC) in an experimental model of acute rejection in small bowel transplantation (SBT).

Material/methods: Heterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad-MSC was intra-arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad-MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad-MSC (TAC_MSC) groups. Each Ad-MSC groups was subdivided in autologous and allogeneic third-party groups.

Results: Rejection rate and severity were similar in MSC-treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T-cell (CD4, CD8, and Foxp3 subsets) and B-cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro- and anti-inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups.

Conclusion: Ad-MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer-term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies.
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April 2021

First steps for the development of silk fibroin-based 3D biohybrid retina for age-related macular degeneration (AMD).

J Neural Eng 2020 10 31;17(5):055003. Epub 2020 Oct 31.

Neuro-computing & Neuro-robotics Research Group, Complutense University of Madrid, Spain. Innovation Research Group, Institute for Health Research San Carlos Clinical Hospital (IdISSC), Madrid, Spain. These authors equally contributed to this article.

Age-related macular degeneration is an incurable chronic neurodegenerative disease, causing progressive loss of the central vision and even blindness. Up-to-date therapeutic approaches can only slow down he progression of the disease.

Objective: Feasibility study for a multilayered, silk fibroin-based, 3D biohybrid retina.

Approach: Fabrication of silk fibroin-based biofilms; culture of different types of cells: retinal pigment epithelium, retinal neurons, Müller and mesenchymal stem cells ; creation of a layered structure glued with silk fibroin hydrogel.

Main Results: In vitro evidence for the feasibility of layered 3D biohybrid retinas; primary culture neurons grow and develop neurites on silk fibroin biofilms, either alone or in presence of other cells cultivated on the same biomaterial; cell organization and cellular phenotypes are maintained in vitro for the seven days of the experiment.

Significance: 3D biohybrid retina can be built using silk silkworm fibroin films and hydrogels to be used in cell replacement therapy for AMD and similar retinal neurodegenerative diseases.
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October 2020

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

Cardiol J 2020 29;27(1):62-71. Epub 2018 Aug 29.

Cardiology Department, Ramón y Cajal University Hospital (IRYCIS), University of Alcalá de Henares, Madrid, Spain.

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure.

Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period.

Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (-5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. -19.7% variation, p < 0.01).

Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.
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June 2021

Experimental model for coadjuvant treatment with mesenchymal stem cells for aortic aneurysm.

Am J Stem Cells 2012 30;1(3):174-81. Epub 2012 Nov 30.

Department of Angiology and Vascular Surgery, La Paz University Hospital Madrid, Spain.

Unlabelled: Many factors are possibly involved in the inflammatory process which causes the degeneration of the arterial wall in the formation of Abdominal Aortic Aneurysms. During the last years different experimental models have been published to treat this fault of the arterial walls. Parallel the clinical treatment has evolved. With this work we have tried to develop an animal model basing on the clinical current treatment. Finally, we propose a treatment based on mesenchymal cells to disable local immune response, preventing excessive fibrosis, apoptosis, and inducing intrinsic cellular progenitors.

Objective: To present a reproducible superior animal model of experimentation, intending to show that mesenchymal stem cells inserted in the sac of an artificial aneurysm are able to survive, so that they can be made accountable for a subsequent beneficial effect upon this condition.

Methods: Six Landrace-White pigs, weighing around 25Kg. We generate 2 aneurysms of abdominal aorta (2x1cm) with Dacron's patches. Later we treat the aneurysms endoscopic with a covered endograft. Finally, in one of the aneurysmal sac we introduce 1cc fibrin sealant and in another 1 cc of fibrin sealant with 10 million MSC. Animals were sacrificed at 24 hs and 1, 3, 5, 7 and 9 weeks. Samples of aneurysms were processed histologically (H&E and Masson). The injected cells were located by immunofluorescence (GFP market).

Results: The surgical technique is reproducible and similar to those conducted in common clinical practice. Histological cross-section samples of cases treated with MSC and analyzed by a blind researcher present a lower inflammation reaction, or with longer evolution time than in controls. Immunofluorescence studies have detected cells marked with GFP up to three weeks after treatment.

Conclusion: This reproducible animal model is similar to common clinical treatment. MSC can stand alive at least for three weeks since their implantation within an aneurysm sac. This may improve the results of conventional endovascular treatment by the stabilization of the aneurysmal sac.
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May 2013