Francisco M. Sánchez-Margallo

Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells

In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell–cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.

Transposition of a pericardial-derived vascular adipose flap for myocardial salvage after infarct.

AIMS Coronary artery occlusion is associated with the risk of ventricular remodelling, heart failure, and cardiogenic shock. Novel strategies are sought to treat these ominous complications. We examined the effect of a pericardial-derived fat flap secured over an acute infarct caused by coronary occlusion. METHODS AND RESULTS A novel intervention consisting of the pericardial isolation of a vascularized adipose flap and its transposition fully covering acute infarcted myocardium was developed in the swine model of coronary artery ligation (n= 52). Left ventricular (LV) ejection fraction and LV end-diastolic and end-systolic volumes were assessed using magnetic resonance imaging (MRI). Infarct size and gene expression analysis were performed on Day 6 and 1 month. Histological changes, collagen volume fraction (CVF), and vascular density were also evaluated on postmortem sections. One month after the intervention, a 18.8% increase in LV ejection fraction (P= 0.007), and significant reductions in LV end-systolic (P= 0.009) and LV end-diastolic volumes (P= 0.03) were found in treated animals compared with the control-MI group. At Day 6, histopathology confirmed a significant infarct size reduction (P= 0.018), the presence of vascular connections at the flap-myocardium interface, and less apoptosis in the infarct border zone compared with control animals (P< 0.001). Up-regulation of genes involved in cell cycle progression, cellular growth and proliferation, and angiogenesis were identified within the flap. CONCLUSIONS Our results indicate that a vascular fat flap exerts beneficial effects on LV function and limits myocardial remodelling. Future studies must confirm whether these findings provide an alternative therapeutic approach for myocardial salvage after infarction.

A preliminary approach to the repair of myocardial infarction using adipose tissue-derived stem cells encapsulated in magnetic resonance-labelled alginate microspheres in a porcine model.

Adipose tissue-derived stem cells (ASCs) have properties of self-renewal, pluripotency and high proliferative capability that make them useful for the treatment of cardiac ventricular function following ischaemic injury. However, their therapeutic use is limited due to the low retention of the cells at the targeted site. To address this issue, we developed semipermeable membrane microcapsules labelled with Endorem (magnetocapsules) that provide mechanical and immunological immune protection to the cells while maintaining internal cell microenvironment. In addition, the particles allow tracking the presence and migration of injected cells in vivo by Magnetic Resonance Imaging (MRI). Results indicate that after 21 days in culture, the cells encapsulated in the magnetocapsules showed similar viabilities than cells encapsulated in conventional microcapsules. MRI confirmed a gradual loss of the intensity of the iron oxide label in the non-encapsulated Endorem labelled cells, while magnetocapsules were detected throughout the study period, suggesting that cell retention in the myocardium is improved when cells are enclosed within the magnetocapsules. To further evaluate treatments effect on global cardiac function, MRI determination of infarct size and left ventricular ejection fraction (LVEF) was performed. In vivo results showed no statistically significant differences in heart rate and cardiac output between treatment groups. In conclusion, cells enclosed within magnetocapsules have shown suitable viability and have been detected in vivo throughout the study period. Further studies will evaluate whether increasing cell loading with the particles may help to improve the therapeutic results.

Tissue consistency perception in laparoscopy to define the level of fidelity in virtual reality simulation

BackgroundWhat degree of fidelity must a laparoscopic simulator have to achieve a training objective? This difficult question is addressed by studying the sensory interaction of surgeons in terms of a surgical skill: tissue consistency perception.MethodsA method for characterizing surgeon sensory interaction has been defined and applied in an effort to determine the relative importance of three components of perceptual surgical skill: visual cues, haptic information, and previous surgical knowledge and experience. Expert, intermediate, and novel surgeons were enrolled in the study. Users were asked to rank tissue consistency in four different conditions: a description of the tissue alone (Q), visual information alone (VI), tactile information alone (TI), and both visual and tactile information (VTI). Agreement between these stages was assessed by a coefficient of determination (R^2).ResultsTissue is a determinant factor (p < 0.001) in the perception of tissue consistency, whereas the expertise of the surgeon is not (p = 0.289). Tissue consistency perception is based mainly on tactile information (TI–VTI agreement is high, R^2 = 0.873), although little sensory substitution is present (VI–VTI agreement is low, R^2 = 0.509). Agreement of Q–VI increases with experience (R^2 = 0.050, 0.290, and 0.573, corresponding with to novel, intermediate, and expert surgeons), which has been associated with the “visual haptics” concept.ConclusionsVirtual reality simulators need haptic devices with force feedback capability if tissue consistency information is to be delivered. On the other hand, the visual haptics concept has been associated with a kind of tactile memory developed by surgical experience.

Augmented Reality for Minimally Invasive Surgery: Overview and Some Recent Advances

Pablo Lamata1,2, Wajid Ali3, Alicia Cano1, Jordi Cornella3, Jerome Declerck2, Ole J. Elle3, Adinda Freudenthal4, Hugo Furtado5, Denis Kalkofen6, Edvard Naerum3, Eigil Samset3, Patricia Sanchez-Gonzalez1, Francisco M. Sanchez-Margallo7, Dieter Schmalstieg6, Mauro Sette8, Thomas Studeli4, Jos Vander Sloten8 and Enrique J. Gomez1 1Universidad Politecnica de Madrid, Spain 2Siemens, United Kingdom 3University of Oslo, Norway 4Delft University of Technology, Netherlands 5Medical Centre Ljubljana, Slovenia 6 Graz University of Technology, Austria 7Minimally Invasive Surgery Centre Jesus Uson, Spain 8University of Leuven, Belgium

Technical feasibility of totally natural orifice cholecystectomy in a swine model

The goal of this study was to evaluate the feasibility of totally NOTES performing a cholecystectomy without laparoscopic assistance. A gastroscope was used through a transvaginal access in five acute female pigs. An incision of 2 cm was created in the vagina and pneumoperitoneum was obtained with a Veress needle. The gallbladder was located in the abdominal cavity using endoscopic transillumination for spatial orientation. After the abdominal suspension of the gallbladder the cholecystectomy was completed with the NOTES technique in four animals without complications. In one animal we had technical problems and the procedure was stopped. The mean operative time was 110 minutes. The transvaginal approach provides complete abdominal exploration and both the cystic duct and artery were identified, clipped, and transected. After dissection the gallbladder was removed through the vagina. Our results showed that completely transvaginal NOTES cholecystectomy is a feasible technique performed only with a flexible endoscope.

Post-infarction scar coverage using a pericardial-derived vascular adipose flap. Pre-clinical results

BACKGROUND Myocardial salvage after coverage with a fat flap was recently demonstrated in acute coronary occlusion. The effect of this novel therapeutic strategy on a chronic myocardial scar is unknown. METHODS Myocardial infarction (MI) was induced by coil deployment in the mid circumflex artery in the swine model. Two weeks after infarction, a pericardial-derived adipose flap was transposed, fully covering the scar, in the treated group. Infarct size and histopathology were analyzed on post mortem sections. To assess cell migration, adenoviral eGFP vectors were injected in the adipose flap and expression was evaluated upon sacrifice both at the flap and myocardium. Magnetic resonance imaging (MRI) was used to measure left ventricular (LV) ejection fraction and ventricular volumes at baseline, 2 weeks post-MI, and at 6 weeks. RESULTS One month after flap transposition, histopathology confirmed a 34% reduction in infarct size (8.7% vs. 5.7%; P=0.04) and the presence of vascular connections at the flap-myocardium interface. High eGFP expression was detected at the infarct core both at the gene and protein level (negligible signal was detected at the flap on sacrifice). At the functional level, changes in LV ejection fraction and volumes (end-systolic and end-diastolic) were not significantly different between groups (all P values>0.1). CONCLUSIONS Our data support the use of post-infarction scar coverage with a pericardial-derived fat flap to reduce infarct size, due partly to neovascular connections and cell trafficking at the flap-myocardium interface. Further studies are needed to validate the functional and clinical relevance of this intervention.

Video-based assistance system for training in minimally invasive surgery.

Abstract In this paper, the development of an assisting system for laparoscopic surgical training is presented. With this system, we expect to facilitate the training process at the first stages of training in laparoscopic surgery and to contribute to an objective evaluation of surgical skills. To achieve this, we propose the insertion of multimedia contents and outlines of work adapted to the level of experience of trainees and the detection of the movements of the laparoscopic instrument into the monitored image. A module to track the instrument is implemented focusing on the tip of the laparoscopic tool. This tracking method does not need the presence of artificial marks or special colours to distinguish the instruments. Similarly, the system has another method based on visual tracking to localize support multimedia content in a stable position of the field of vision. Therefore, this position of the support content is adapted to the movements of the camera or the working area. Experimental results are presented to show the feasibility of the proposed system for assisting in laparoscopic surgical training.

Ergonomic Assessment of Hand Movements in Laparoscopic Surgery Using the CyberGlove

The main objective of this chapter is the automation of the ergonomic assessment of the wrist’s positions, through biomechanics analysis techniques, specifically using the rapid upper limb assessment (RULA). So, this allows establishing new use and design guidelines of the laparoscopic instruments, in order to reduce the influence of risk factors in the wrist area, which are associated with forced positions during the development of laparoscopic activities.

Adult hydrocele and spermatocele.

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