Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells

Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI

Microglia Stimulation by Protein Extract of Injured Rat Spinal Cord. A Novel In vitro Model for Studying Activated Microglia

Research on microglia has established the differentiation between the so-called M1 and M2 phenotypes. However, new frameworks have been proposed attempting to discern between meaningful microglia profiles. We have set up an in vitro microglial activation model by adding an injured spinal cord (SCI) lysate to microglial cultures, obtained from postnatal rats, in order to mimic the environment of the spinal cord after injury. We found that under the presence of the SCI lysate microglial cells changed their phenotype, developing less ramified but longer processes, and proliferated. The SCI lysate also led to upregulation of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, downregulation of the anti-inflammatory cytokines IL-10 and IL-4, and a biphasic profile of iNOS. In addition, a latex beads phagocytosis assay revealed the SCI lysate stimulated the phagocytic capacity of microglia. Flow cytometry analysis indicated that microglial cells showed a pro-inflammatory profile in the presence of SCI lysate. Finally, characterization of the microglial activation in the spinal cord on day 7 after contusion injury, we showed that these cells have a pro-inflammatory phenotype. Overall, these results indicate that the use of SCI lysates could be a useful tool to skew microglia towards a closer phenotype to that observed after the spinal cord contusion injury than the use of LPS or IFNγ

Effects of the post-spinal cord injury microenvironment on the differentiation capacity of human neural stem cells derived from induced pluripotent stem cells

This work was supported by TERCEL and CIBERNED funds from the Instituto de Salud Carlos III of Spain, and FEDER funds from the EC.Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site

Regulació de les metal·lotioneïnes hepàtiques i cerebrals

Descripció del recurs: el 21 setembre 2011Penden

Activation of lysophosphatidic acid receptor type 1 (LPA1) contributes to pathophysiology of spinal cord injury

Altres ajuts: NIH/NS084398Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1-LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptor-mediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA-LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injur

Interdigitated back-contacted crystalline silicon solar cells fully manufactured with atomic layer deposited selective contacts

The interdigitated back-contacted (IBC) solar cell concept has been extensively studied for single-junction cells and more recently as a good choice for three-terminal tandem devices. In this work, carrier-selective contacts based on transition metal oxides deposited by atomic layer deposition (ALD) technique are applied to IBC c-Si(n) devices. In the first part of the study, we develop a hole-selective contact based on thin ALD vanadium oxide (V2O5) layers without using an amorphous silicon interlayer. The ALD process has been optimised, i.e. number of ALD cycles and deposition temperature, as a trade-off between surface passivation and contact resistivity. Noticeable surface passivation with recombination current densities around 100 fA/cm2, as well as reasonable contact resistivity values below 250 mOcm2 are reached using 200 ALD V2O5 cycles deposited at a deposition temperature of 125 °C (~10 nm layer thickness). The optimised ALD V2O5-based contact is combined with both an ALD TiO2-based electron-selective contact and an excellent surface passivation in non-contacted regions provided by ALD Al2O3 films, to form a fully ALD IBC c-Si(n) solar cell scheme. Fabricated devices yield photovoltaic efficiencies and pseudo efficiencies, i.e. calculated without series resistance losses, of 18.6% and 21.1% respectively (3 cm × 3 cm device area). These results reveal the potential of the ALD technique to deposit transition metal oxide (TMO) films as selective contacts on high efficiency devices, paving the way of using low thermal-budget, low cost and highly scalable processes for a highly demanding IBC solar cell architecture in the photovoltaic industry.Peer ReviewedPostprint (updated version

Atomic layer deposition of vanadium oxide films for crystalline silicon solar cells

Transition metal oxides (TMOs) are promising materials to develop selective contacts on high-efficiency crystalline silicon solar cells. Nevertheless, the standard deposition technique used for TMOs is thermal evaporation, which could add potential scalability problems to industrial photovoltaic fabrication processes. As an alternative, atomic layer deposition (ALD) is a thin film deposition technique already used for dielectric deposition in the semiconductor device industry that has a straightforward up scalable design. This work reports the results of vanadium oxide (V2O5) films deposited by ALD acting as a hole-selective contact for n-type crystalline silicon (c-Si) solar cell frontal transparent contact without the additional PECVD passivating layer. A reasonable specific contact resistance of 100 mO cm2 was measured by the transfer length method. In addition, measurements suggest the presence of an inversion layer at the c-Si/V2O5 interface with a sheet resistance of 15 kO sq-1. The strong band bending induced at the c-Si surface was confirmed through capacitance–voltage measurements with a built-in voltage value of 683 mV. Besides low contact resistance, vanadium oxide films provide excellent surface passivation with effective lifetime values of up to 800 µs. Finally, proof-of-concept both-side contacted solar cells exhibit efficiencies beyond 18%, shedding light on the possibilities of TMOs deposited by the atomic layer deposition technique.Peer ReviewedObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (updated version

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride and sterol classes) were also linked with obesity traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.Supported by Centro para el Desarrollo Tecnológico e Industrial, Spain, Project reference: IPT-20111008, and Generalitat de Catalunya grants 2017SGR1719 and 2017SGR696. MJ is a "Serra Hunter" program fellow. Supported by Instituto de Salud Carlos III, Spain, Project reference: 17-00134, co-financed by FEDER Funds A way to make Europe

Expanding the perspective of polymeric selective contacts in photovoltaic devices using branched polyethylenimine

This work studies the use of polymeric layers of polyethylenimine (PEI) as an interface modification of electron-selective contacts. A clearly enhanced electrical transport with lower contact resistance and significant surface passivation (about 3 ms) can be achieved with PEI modification. As for other conjugated polyelectrolytes, protonated groups of the polymer with their respective counter anions from the solvent create an intense dipole. In this work, part of the amine groups in PEI are protonated by ethanol that behaves as a weak Brønsted acid during the process. A comprehensive characterization including high-resolution compositional analysis confirms the formation of a dipolar interlayer. The PEI modification is able to eliminate completely Fermi-level pinning at metal/semiconductor junctions and shifts the work function of the metallic electrode by more than 1 eV. Induced charge transport between the metal and the semiconductor allows the formation of an electron accumulation region. Consequently, electron-selective contacts are clearly improved with a significant reduction of the specific contact resistance (less than 100 mO·cm2). Proof-of-concept dopant-free solar cells on silicon were fabricated to demonstrate the beneficial effect of PEI dipolar interlayers. Full dopant-free solar cells with conversion efficiencies of about 14% could be fabricated on flat wafers. The PEI modification also improved the performance of classical high-efficiency heterojunction solar cells.This research has been supported by the Spanish government through Grants PID2019-109215RB-C41, PID2019109215RB-C43, PID2020-115719RB-C21, and PID2020116719RB-C41 and funded by MCIN/AEI/10.13039/ 501100011033. Besides this the authors would like to thank Prof. Jordi LLorca for his expertise and helpful discussions of XPS results, as well as Dr. Rodrigo Fernández-Pacheco of the Laboratorio de Microscopias Avanzadas (LMA-INA) of Zaragoza for the HRTEM images and EDS and EELS analysis, and Guillaume Sauthier from ICN2 for his contribution through UPS measurements and discussions.Peer ReviewedPostprint (published version