JUMISC

NANOMEDICINE APPLICATIONS IN DRUG DELIVERY AND TARGETING: NANBIOSIS – NANOMED Industrial Forum

Yesterday took place in Barcelona, at Barcelona School of Management, Universitat Pompeu Fabra, a meeting of resarch groups and units of NANBIOSIS and CIBER-BBN and companies in the third B2B Forum organized by NANBIOSIS, in this case together with NANOMED SPAIN.

Thirteen companies and twelve groups from CIBER-BBN and CCMIJU (ten of them coordinating NANBIOSIS units) got together to explain, through short presentations of ten minutes, those lines of their work aimed at finding synergies and potential collaborations in the area of Nanomedicine apllications in drug delivery and targeting. There was also a talk by a representative of CDTI (Spanish National Center for Industrial and Technological Development) to explain the financing opportunities for the companies as well as a presentation by the NANBIOSIS Coordinator, Jesús Izco, to show the new Cutting Edge Biomedical Solutions offered by the ICTS-NANBIOSIS.

After lunch, the groups and companies had the opportunity to discuss in more detail, during bilateral interviews coordinated by NANBIOSIS a, those aspects that had attracted their attention, as well as, in some cases, to draw potential collaborations. The event was successfully developed with 45 attendees and more than 50 individual B2B mettings.

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NANBIOSIS working on the development of next generation catheters

NANBIOSIS’ partners CIBER-BBN and JUMISC, with another 44 European partners, led by Philips Electronics Nederland B.V, will work on the development of next genration catheters.

The project, Position-II (Ref. n. 783132), that pretends to diversify the production of smart catheters (overcoming the obsolescence of current ones), improve their performance (facilitating their use to be smaller), reduce current production costs and break existing monopolies, has been submitted to the Call for Electronic Components and Systems for European Leadership (ECSEL)- Horizon 2020, with a duration of three years -starting on 1/6/18- and with a budget of over €41M, (€10.4M-financed by European Union)

The objective of the participation of JUMISC in Position-II is to develop new catheters that, in combination with hydrogels and cell therapy, will have a regenerative effect to stimulate the recovery of cardiac areas damaged by heart attacks. NANBIOSIS U10. Drug Formulation, of CIBER-BBN, at UPV-EHU, coordinated by José Luis Pedraz and Jsús Ciriza, will microencapsulate the cells to be test and administered in porcine model at the JUMISC to validate the designed catheter.

The kick-off of the Eurpean project under Grant Agreement Ecsel-783132- POSOTION II 2017-IA took place on June 5 to 7 in Rotterdam, representatives of the NANBIOSIS-ICTS Steering Committee, unit 10 and unit 24 were present.

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Intestinal histopathological changes in a porcine model of pneumoperitoneum-induced intra-abdominal hypertension

Francisco Miguel Sánchez Margallo, Scientific Director of JUMISC, is co-author of the publication “Intestinal histopathological changes in a porcine model of pneumoperitoneum-induced intra-abdominal hypertension” by Surgical Endoscopy.

The study was performed with the participation of NANBIOSIS Units: U21-Experimental operating rooms, and U22-Animal housing. and showed that the evolution of intestinal injuries from pneumoperitoneum-induced IAH depends on the degree of IAP, these damages may be associated with decreases in APP and pH_i, and increases in Lc

For further information: click here

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Interpretation of motion analysis of laparoscopic instruments based on principal component analysis in box trainer settings

Francisco Miguel Sánchez Margallo, Scientific Director of CCMIJU and NANBIOSIS U21. Experimental operating rooms, is co-author of the publication “Interpretation of motion analysis of laparoscopic instruments based on principal component analysis in box trainer settings” published by Surgical Endoscopy

The study results show that three new HSMAPs per hand were defined for PG and PC tasks, and two per hand for KS task. PG presented validity for HSMAPs related to insecurity and economy of space. PC showed validity for HSMAPs related to cutting efficacy, peripheral unawareness, and confidence. Finally, KS presented validity for HSMAPs related with economy of space and knotting securitya. Thus, PCA-defined HSMAPs can be used for technical skills’ assessment. Construct validation and expert knowledge can be combined to infer how competences are acquired in box trainer tasks. These findings can be exploited to provide residents with meaningful feedback on performance. Future works will compare the new HSMAPs with valid scoring systems such as GOALS.

The study has been develloped with surgical facilities of high technology that allow in vivo efficacy assays of drugs, nanomedicines, biomaterials and others, performed at unit 21 of NANBIOSIS.

Article of reference: Oropesa, I., Escamirosa, F.P., Sánchez-Margallo, J.A. et al. Surg Endosc (2018) 32: 3096. https://doi.org/10.1007/s00464-018-6022-6

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Evaluation of a New Design of Antireflux-Biodegradable Ureteral Stent in Animal Model

Francisco Miguel Sánchez Margallo, Assistant Director of NANBIOSIS and Scientific Director of JUMISC, is co-authors of de article “Evaluation of a New Design of Antireflux-biodegradable Ureteral Stent in Animal Model” published by Urology.

The research were carried out in the NANBIOSIS units in the JUMISC. The purpose was to determine the effects in urinary tract of a new antireflux-biodegradable ureteral stent. Thirty six ureters belonging to 24 pigs were used. The study began with endoscopic, nephrosonographic, and fluoroscopic assessments. Three study groups of ureters (n = 12) were then specified. In group I, a biodegradable antireflux ureteral stent (BDG-ARS) was inserted in the right ureter of 12 pigs. Group II comprised the left ureter of the same animals, in which a double-pigtail stent was placed for 6 weeks. Group III ureters, belonging to 12 additional animals, were subjected to a ureteropelvic junction obstruction model that was then treated by endopyelotomy and stenting with BDG-ARS. Follow-ups were performed at 3-6 weeks and at 5 months. As result of the research none of the ureters receiving the BDG-ARS showed any evidence of vesicoureteral reflux (VUR). BDG-ARS degradation took place in a controlled and predictable fashion from the third to the sixth weeks, and no obstructive fragments appeared. No differences were found between groups I and II regarding passive ureteral dilation, but significant differences were found regarding VUR and ureteral orifice damage. BDG-ARS always maintained distal ureteral peristalsis. BDG-ARS in group III showed a 50% positive urine culture rate and a 16.6% migration rate in both BDG-ARS groups.

The scientists have demonstrated that morbidity associated with ureteral stents might be reduced as BDG-ARS avoided VUR and bladder trigone irritation, and the polymer combination and stent-braided design achieved a consistent biodegradation rate with no obstructive fragments and with uniform degradation between the third and the sixth weeks. Consequently, morbidity associated with ureteral stents might be reduced.

DOI: 10.1016/j.urology.2018.02.004

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Relevant research results for assisted reproduction.

Javier García Casado, Scientific Director of NANBIOSIS Unit 14: Cell therapy toguether with other Scientists of NANBIOSIS and CCMIJU have issued the first report describing the beneficial effect of human EV-endMSCs on embryo development, which has been recently published by PloS One: “Murine embryos exposed to human endometrial MSCs-derived extracellular vesicles exhibit higher VEGF/PDGF AA release, increased blastomere count and hatching rates“. The results could be relevant for assisted reproduction:

“Endometrial Mesenchymal Stromal Cells (endMSCs) are multipotent cells with immunomodulatory and pro-regenerative activity which is mainly mediated by a paracrine effect. The exosomes released by MSCs have become a promising therapeutic tool for the treatment of immune-mediated diseases. More specifically, extracellular vesicles derived from endMSCs (EV-endMSCs) have demonstrated a cardioprotective effect through the release of anti-apoptotic and pro-angiogenic factors. Here we hypothesize that EV-endMSCs may be used as a co-adjuvant to improve in vitro fertilization outcomes and embryo quality. Firstly, endMSCs and EV-endMSCs were isolated and phenotypically characterized for in vitro assays. Then, in vitro studies were performed on murine embryos co-cultured with EV-endMSCs at different concentrations. Our results firstly demonstrated a significant increase on the total blastomere count of expanded murine blastocysts. Moreover, EV-endMSCs triggered the release of pro-angiogenic molecules from embryos demonstrating an EV-endMSCs concentration-dependent increase of VEGF and PDGF-AA. The release of VEGF and PDGF-AA by the embryos may indicate that the beneficial effect of EV-endMSCs could be mediating not only an increase in the blastocyst’s total cell number, but also may promote endometrial angiogenesis, vascularization, differentiation and tissue remodeling”.

Soluble factors were analyzed by the ICTS Nanbiosis (Unit 14. Cell therapy at CCMIJU). Maintenance of animals was performed by the ICTS Nanbiosis (Unit 22. Animal housing at CCMIJU). In vivo embryo recovery and culture was performed by the ICTS Nanbiosis (Unit 23. Assisted Reproduction at CCMIJU)

Article of reference:

Blázquez R, Sánchez-Margallo FM, Álvarez V, Matilla E, Hernández N, Marinaro F, Gómez-Serrano M, Jorge I, Casado JG, Macías-García B. “Murine embryos exposed to human endometrial MSCs-derived extracellular vesicles exhibit higher VEGF/PDGF AA release, increased blastomere count and hatching rates”. PLoS One (2018-04; vol. 13(4))

DOI: 10.1371/journal.pone.0196080

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Oocyte holding in the Iberian red deer: Effect of initial oocyte quality and epidermal growth factor addition on in vitro maturation

José Mijares Gordún, and Francisco M. Sánchez Margallo, Scientific Director and Scientific Coordinator of NANBIOSIS U23. Asisted Reproduction, are co-authors of de article “Oocyte holding in the Iberian red deer (Cervus elaphus hispanicus): Effect of initial oocyte quality and epidermal growth factor addition on in vitro maturation“, published by Reproduction in Domestic Animals.

The scientists have demonstrated that oocyte holding can be used in Iberian red deer oocytes. Interestingly, EGF addition increases the oocytes’ meiotic competence in immediately matured oocytes but not after oocyte holding depending upon initial oocyte quality.

The investigation has been continued in the assisted reproduction laboratory of unit 23 of NANBIOSIS, equipped with two intracitoplasmatic micromanipulation equipment of the latest generation with IMSI, Laser and Oosight system, embryo biopsy systems, vision systems of the mitotic spindle, with flow cabinets with stereo-microscopes and heated plates, incubators with different gasses systems, equipment and cryopreservation freeze gamete and embryo, among others.

For further information: DOI: 10.1111/rda.13099

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Mesenchymal stem cells or exosomes with fibrin glue mesh fixation modulates the inflammatory reaction in a murine model of incisional hernia

Javier García Casado, Scientific Director of NANBIOSIS U14, Cell Therapy Unit, and Francisco Miguel Sánchez Margallo, Scientific Director of CCMIJU, are co-author of the publication “Fibrin glue mesh fixation combined with mesenchymal stem cells or exosomes modulates the inflammatory reaction in a murine model of incisional hernia” by Acta Biomaterialia.

In vitro experiments were performed by the ICTS Nanbiosis (Unit 14. Cell therapy at CCMIJU). Exosomes characterization was performed by the ICTS Nanbiosis (Unit 6: Biomaterial processing and Nanostructuring Unit). In vivo experiments were performed by the ICTS Nanbiosis (Unit 22. Animal housing at CCMIJU).

The study has demonstrated a significant increase of anti-inflammatory M2 macrophages and TH2 cytokines when MSCs or exo-MSCs were used. Moreover, the analysis of MMPs, TIMPs and collagen exerted significant differences in the extracellular matrix and in the remodeling process. The in vivo study suggests that the fixation of surgical meshes with FG and MSCs or exo-MSCs will have a beneficial effect for the treatment of incisional hernia in terms of improved outcomes of damaged tissue, and especially, in the modulation of inflammatory responses towards a less aggressive and pro-regenerative profil,

The implantation of surgical meshes is the standard procedure to reinforce tissue defects such as hernias. However, an exacerbated and persistent inflammatory response secondary to this implantation is frequently observed, leading to a strong discomfort and chronic pain in the patients. In many cases, an additional surgical intervention is needed to remove the mesh.

This study shows that mesenchymal stem cells and their exosomes, combined with a fibrin sealant, can be used for the successful fixation of these meshes. This new therapeutic approach, assayed in a murine model of incisional hernia, favors the modulation of the inflammatory response towards a less aggressive and pro-regenerative profile

For further information: DOI: https://doi.org/10.1016/j.actbio.2018.02.014.

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Laparoendoscopic Single-Site Surgery Using Handheld Robotic Device

Francisco Miguel Sánchez Margallo, Scientific Director of CCMIJU and NANBIOSIS U21. Experimental operating rooms, is co-author of the publication “Assessment of Postural Ergonomics and Surgical Performance in Laparoendoscopic Single-Site Surgery Using a Handheld Robotic Device“, by Surgical Innovation (SAGE journal).

The study results show a positive learning curve in ergonomics and surgical performance using the robotic instrument during LESS surgery. This instrument improves the surgeon’s body posture and the needle positioning errors. The use of the robotic instrument is feasible and safe during LESS partial nephrectomy and sigmoidectomy procedures.

The study has been develloped with surgical facilities of high technology that allow in vivo efficacy assays of drugs, nanomedicines, biomaterials and others, performed at unit 21 of NANBIOSIS.

For further information: DOI: 10.1177/1553350618759768

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CCMIJU, partner of NANBIOSIS and the Real Academia Nacional de Medicina sign a scientific cooperation agreement

The Real Academia Nacional de Medicina and the Centro de Cirugía de Mínima Invasión Jesús Usón, located in Cáceres, have signed a cooperative agreement in the field of training and cooperative R&D projects.

Last 24^th April, Professor Joaquín Poch Broto, President of the Real Academia Nacional de Medicina (RANM) and Mr. Luis Casas Luengo, the CCMIJU’s Managing Director, met at Madrid to sign a cooperative agreement.

This event, held at the Yellow Room of the Academia, counted on Prof. Vicente Calatayud (Academic Member), Prof. Luis Pablo Rodríguez (General Secretary), Dr. Francisco Miguel Sánchez Margallo (CCMIJU’s Scientific Director), and its founder, Prof. Usón Gargallo (Honorary President).

On one hand, this agreement focuses on training, mobility, stays, grants… and on the other hand, on didactic activities, carrying out postgrad courses and seminars. It includes the cooperation in R&D projects, specifically in all related to the development of new materials, tools, equipment and new systems in the health field.

The signing considers the cooperation with other companies and research institutes to promote and improve the training of the physicians.

The RANM promotes and carries out activities to develop medicine and spreads its results for the application to society. On 13^th March, Academy agreed to support CCMIJU’s candidacy to Princesa de Asturias Awards, in International Category.

The CCMIJU is devoted to research, training and innovation. From 2014 it is one of the 29 existing Singular Scientific Technological Infrastructure (ICTS) in Spain.

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