generation-of-functional-endodermal-hepatic-organoids

Generation of Functional Endodermal Hepatic Organoids

Organoid technology has allowed us to generate a variety of human organ-like mini structures, such as for the liver, brain, and intestine, in vitro. The ...

Izmir Biomedicine and Genome Center

Dokuz Eylul University

The aim of this study was to investigate the effects of intrathecally administered ketorolac tromethamine on ultrastructural changes of the spinal cord in spinal cord-traumatised rats.

Neuroprotective effects of ketorolac tromethamine after spinal cord injury in rats: an ultrastructural study.

Increased arginase activity in the airways induces reduced bioavailability of L-arginine and cause deficiency of bronchodilatating and anti-inflammatory nitric oxide (NO). Therefore, arginine and arginase inhibitors may have therapeutic potential in the treatment of asthma. Using a murine model of asthma, we aimed to investigate the effects of inhaled L-arginine and arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) and co-treatment on airway histology of asthmatic lung tissue.

Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma.

Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO) in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂) and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control). All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I), saline (Group II) and budesonide (Group III), respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL) was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043). Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05). Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

Effects of inhaled L-arginine administration in a murine model of acute asthma.

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling.

We aimed to compare the local effects of intracameral cefuroxime diluted in normal saline (SF groups) against those of cefuroxime in balanced salt solution (BSS group) on the cornea of rabbits.

Comparison of the local effects of different intracameral cefuroxime solutions on rabbit cornea.

Alzheimer's disease is a chronic and progressive neurodegenerative disorder, which is the most common cause of dementia worldwide. Although amyloid plaques and neurofibrillary tangles are identified as the hallmarks of the disease, the only valid diagnostic method yet is post-mortem imaging of these molecules in brain sections. Exosome is a type of extracellular vesicles secreted into extracellular space and plays fundamental roles in healthy and pathological conditions, including cell-to-cell communication. In this study, we aimed to investigate the proteomic contents of neuron-derived exosomes (NDEs) from AD patients and healthy controls (HCs) to identify a possible marker for AD diagnosis. We identified alpha-globin, beta-globin, and delta-globin increase in neuron-derived exosomes of AD patients compared to HCs with LC-MS/MS proteomics analysis. Then, we confirmed the high hemoglobin (Hb) level in NDEs of AD patients with ELISA. We found the area under the curve of hemoglobin level as 0.6913 with ROC analysis. Cargo proteins of NDEs may be useful diagnostic biomarker for AD.

Proteome profiling of neuron-derived exosomes in Alzheimer's disease reveals hemoglobin as a potential biomarker.

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model.

The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts.

Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts.

Burn wounds are frequently encountered health problems, which need a new treatment approach especially in terms of good patient compliance. Availability of use of antioxidant agents and bio-adhesive gels in tissue healing can be an alternative as a new approach for wound healing. Antioxidant taurine containing bio-adhesive gels were prepared by using carbopol (CP) 940 and 934. Rheological and texture analyses were carried out on bio-adhesive gels for in vitro characterization. Wound model on Wistar rats was used to evaluate the in vivo evaluation of gels. Rheological and texture analyses showed that a carbopol bioadhesive gel has acceptable topically use dosage characteristics and in combination with Taurine it presented a successful wound healing effect via antioxidant parameters. In conclusion, bio-adhesive CP 940 (2%) gel containing 50 mM taurine could be promising in the treatment of burns by balancing oxidative stress.

Article	Year
Neuroprotective effects of ketorolac tromethamine after spinal cord injury in rats: an ultrastructural study. Advances in therapy\| PubMed ID: 18297253	2008
Beneficial effects of arginase inhibition and inhaled L-arginine administration on airway histology in a murine model of chronic asthma. Allergologia et immunopathologia\| PubMed ID: 23578782	2014
Effects of inhaled L-arginine administration in a murine model of acute asthma. Iranian journal of allergy, asthma, and immunology\| PubMed ID: 25150072	2014
Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling. Stem cell reports\| PubMed ID: 31522975	2019
Comparison of the local effects of different intracameral cefuroxime solutions on rabbit cornea. Cutaneous and ocular toxicology\| PubMed ID: 32854557	2020
Proteome profiling of neuron-derived exosomes in Alzheimer's disease reveals hemoglobin as a potential biomarker. Neuroscience letters\| PubMed ID: 33901610	2021
Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model. Journal of biophotonics\| PubMed ID: 34529359	2022
Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts. Journal of diabetes and its complications\| PubMed ID: 36905721	2023
Design and in vitro, in vivo evaluation of antioxidant bioadhesive gels for burn treatment. Turkish journal of biology = Turk biyoloji dergisi\| PubMed ID: 37529259	2022

Alper Bagriyanik

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