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Neurovascular unit on a chip:the relevance and maturity as an advanced in vitro model

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Neural Regeneration Research 2024年第6期19卷 1165-1166页

作者： Sujey Palma-Florez Anna Lagunas Mònica Mir Nanobioengineering Group Institute for Bioengineering of Catalonia(IBEC)Barcelona Institute of Science and Technology(BIST)BarcelonaSpain ciber-BBN ISCIIIMadridSpain Department of Electronics and Biomedical Engineering University of BarcelonaBarcelonaSpain

The brain is a high-energy demanding organ,consuming around 20%of the metabolic energy *** fulfill this demand,cerebral blood flow(CBF)supplies oxygen and glucose continuously through the intricate network of cerebral blood *** for many years brain activity and blood flow were conceived as independent processes,MRI-based functional brain imaging demonstrated that there is a coupling between them.

关键词： cerebral maturity consuming

Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering

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Neural Regeneration Research 2020年第5期15卷 783-789页

作者： Rocío Fernández-Serra Rebeca Gallego Paloma Lozano Daniel González-Nieto Center for Biomedical Technology Universidad Politécnica de Madrid. MadridSpain Departamento de Tecnología Fotónica y Bioingeniería ETSI TelecomunicacionesUniversidad Politécnica de MadridMadridSpain Biomedical Research Networking Center in bioengineering Biomaterials and Nanomedicine (ciber-BBN) MadridSpain

The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal ***-performance preclinical results have failed at clinical level,as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke,Alzheimer’s and Parkinson’s *** unquestionable reality is the current absence of effective therapies to neuroprotect the brain,to arrest neurodegeneration and rewire the impaired brain *** of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet *** contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation *** medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last *** the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs,the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown ***-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced *** show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and *** is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and *** this article,we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery,cell engraftment and axonal reinnervation in brain p

关键词： advanced therapies Alzheimer’s disease biomaterials brain hydrogels neurological diseases Parkinson’s disease polymers stroke

Biotinylated polyurethane-urea nanoparticles for targeted theranostics in human hepatocellular carcinoma

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Nano Research 2015年第5期8卷 1729-1745页

作者： Genoveva MorraI-Ruiz Pedro Melgar-Lesmes Andrea Lopez-Vicente Conxita Solans Maria Jose Garcia-Celma Department of Pharmacy and Pharmaceutical Technology Faculty of Pharmacy University of Barcelona Av Joan XXIII s/n 08028 Barcelona Spain Institute of Advanced Chemistry of Catalonia (IQAC) CS/C Jordi Girona 18-26 08034 Barcelona Spain Networking Research Center on bioengineering Biomaterials and Nanomedicine CIBER-BBN Spain

Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110-145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.

关键词： cancer therapy DNA nanoparticles polyurethane theranostics

Tracking of iron-labeled human neural stem cells by magnetic resonance imaging in cell replacement therapy for Parkinson＇s disease

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Neural Regeneration Research 2016年第1期11卷 49-52页

作者： Milagros Ramos-Gómez Alberto Martínez-Serrano Centre for Biomedical Technology Polytechnic University of Madrid Madrid Spain Biomedical Research Networking'Center of bioengineering Biomaterials and Nanomedicine (ciber-BBN) Madrid Spain Department of Molecular Biology and Center of Molecular Biology"Severo Ochoa" Autonomous University of Madrid-C.S.I.C Madrid Spain

Human neural stem cells（h NSCs） derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson＇s disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time.

关键词： human neural stem cells Parkinson's disease magnetic resonance imaging magnetic nanoparticles stem cell transplantation

Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components--Guidance of the inflammatory response as basis for osteochondral regeneration

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Bioactive Materials 2017年第4期2卷 208-223页

作者： Mike Barbeck Tiziano Serra Patrick Booms Sanja Stojanovic Stevo Najman Elisabeth Engel Robert Sader Charles James Kirkpatrick Melba Navarro Shahram Ghanaati Private Office BerlinGermany Institute for bioengineering of Catalonia(IBEC) Biomaterials for Regenerative MedicineBarcelonaSpain Clinic of Oro-Maxillofacial and Plastic Surgery FORM-LabGoethe University FrankfurtFrankfurtGermany University of Ni's Faculty of MedicineDepartment for Cell and Tissue EngineeringInstitute of Biology and Human GeneticsNi'sSerbia Technical University of Catalonia(UPC) Dpt.Materials Science and MetallurgySpain ciber en Bioingenieria Biomateriales y Nanomedicina(CIBER-BBN)Spain

The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the(molecular)weight loss and the morphological and mechanical variations after immersion in *** in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical *** scaffold parts kept their structural integrity,while changes in morphology were observed,especially for the PLA/G5 *** properties decreased with progressive degradation,while the PLA/G5 scaffolds presented higher compressive modulus than PLA *** tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds,while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed *** revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 ***,the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical ***,the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs,while within the PLA parts a significantly lower vascularization was found optimally for chondral ***,this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue ***,the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.

关键词： Bioactive glass Polylactic acid(PLA) Bi-layer scaffold Multinucleated giant cells Bone substitute Vascularization Calcium phosphate glass

Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

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Neural Regeneration Research 2018年第2期13卷 239-240页

作者： ivan fernandez-bueno yolanda diebold instituto universitario de oftalmobiología aplicada university of valladolidValladolidSpain red temática de investigación cooperativa en salud(retics) oftaredinstituto de salud carlos IIIMadridSpain biomedical research networking center on bioengineering biomaterials and nanomedicineciber-bbnValladolidSpain

Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.

关键词： Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

Long-term in vivo single-cell lineage tracing of deep structures using three-photon activation

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Light(Science & Applications) 2016年第1期5卷 730-736页

作者： Isil Tekeli Isabelle Aujard Xavier Trepat Ludovic Jullien Angel Raya Dobryna Zalvidea Center of Regenerative Medicine in Barcelona(CMRB) Barcelona Biomedical Research ParkDr Aiguader 8808003 BarcelonaSpain Control of Stem Cell Potency Group Institute for Bioengineering of Catalonia(IBEC)Barcelona Science ParkBaldiri Reixac 15-2108028 BarcelonaSpain École Normale Supérieure-PSL Research University Department of Chemistry24 rue LhomondF-75005 ParisFrance Sorbonne Universités UPMC Univ Paris 06PASTEURF-75005 ParisFrance CNRS UMR 8640 PASTEURF-75005 ParisFrance Integrative Cell and Tissue Dynamics Group Institute of Bioengineering of Catalonia(IBEC)08028 BarcelonaSpain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) 08010 BarcelonaSpain Center for Networked Biomedical Research on bioengineering Biomaterials and Nanomedicine(CIBER-BBN)28029 MadridSpain

Genetic labeling techniques allow for noninvasive lineage tracing of cells in ***-photon inducible activators provide spatial resolution for superficial cells,but labeling cells located deep within tissues is precluded by scattering of the far-red illumination required for two-photon ***-photon illumination has been shown to overcome the limitations of two-photon microscopy for in vivo imaging of deep structures,but whether it can be used for photoactivation remains to be *** we show,both theoretically and experimentally,that three-photon illumination overcomes scattering problems by combining longer wavelength excitation with high uncaging three-photon cross-section *** prospectively labeled heart muscle cells in zebrafish embryos and found permanent labeling in their progeny in adult animals with negligible tissue *** technique allows for a noninvasive genetic manipulation in vivo with spatial,temporal and cell-type specificity,and may have wide applicability in experimental biology.

关键词： multi-photon microscopy photoactivation three-photon microscopy zebrafish

Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics

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Cancer Drug Resistance 2021年第1期4卷 44-68页

作者： Anna Ulldemolins Joaquin Seras-Franzoso Fernanda Andrade Diana Rafael Ibane Abasolo Petra Gener Simo Schwartz Jr Drug Delivery and Targeting Group Molecular Biology and Biochemistry Research Centre for Nanomedicine(CIBBIM-Nanomedicine)Vall d’Hebron Institut de RecercaUniversitat Autonoma de BarcelonaBarcelona 08035Spain Networking Research Centre for bioengineering Biomaterialsand Nanomedicine(CIBER-BBN)Instituto de Salud Carlos IIIZaragoza 50009Spain

Advanced cancer is still considered an incurable disease because of its metastatic spread to distal organs and progressive gain of *** though considerable treatment progress and more effective therapies have been achieved over the past years,recurrence in the long-term and undesired side effects are still the main drawbacks of current clinical ***,a majority of chemotherapeutic drugs are highly hydrophobic and need to be diluted in organic solvents,which cause high toxicity,in order to reach effective therapeutic *** limitations of conventional cancer therapies prompted the use of nanomedicine,the medical application of nanotechnology,to provide more effective and safer cancer *** of nanomedicines to overcome resistance,ameliorate solubility,improve pharmacological profile,and reduce adverse effects of chemotherapeutical drugs is thus highly *** use in the clinical setting has increased over the last *** the various existing nanosystems,nanoparticles have the ability to transform conventional medicine by reducing the adverse effects and providing a controlled release of therapeutic ***,their small size facilitates the intracellular ***,we provide a closer review of clinical prospects and mechanisms of action of nanomedicines to overcome drug *** significance of specific targeting towards cancer cells is debated as well.

关键词： Drug delivery systems resistance nanomedicine cancer treatment

Hypoglycemia associated with fluoxetine treatment in a patient with type 1 diabetes

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World Journal of Clinical Cases 2013年第5期1卷 169-171页

作者： Betina Biagetti Rosa Corcoy Servei d’Endocrinologia i Nutrició Hospital de la Santa Creu i Sant Pau Avgda Sant Antoni M Claret 167 08025 Barcelona Spain Departament de Medicina Universitat Autònoma de Barcelona 08193 Belllaterra Spain ciber bioengineering Biomaterials and Nanotechnology Instituto de Salud Carlos Ⅲ 28029 Madrid Spain

We report on a patient with type 1 diabetes mellitus who presented with recurrent episodes of hypoglycemia and a marked reduction in her daily insulin requirements after introduction of fluoxetine. This 25-yearold Caucasian woman had been followed up at the outpatient clinic for type 1 diabetes mellitus and prepregnancy care. She used a continuous subcutaneous insulin infusion with lispro and her daily insulin dose was 0.5 IU/kg per day. She had no chronic diabetic complications or hypoglycemia unawareness. Fluoxetine at a daily dose of 20 mg had been started because of depressive symptoms and within one week, she presented recurrent hypoglycemic episodes that prompted a progressive reduction in the insulin dose down to 0.3 IU/kg per day. The reduced insulin requirements continued during the period of fluoxetine treatment while glycated hemoglobin remained stable. She had no concurrent additional cause to explain the reduced insulin requirements. After fluoxetine was stopped, insulin re-quirements progressively increased and returned to the patient′s usual dose.

关键词： Fluoxetine Selective serotonin-reuptake inhibitor Hypoglycemia Diabetes mellitus