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Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

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Neural Regeneration Research 2020年第3期15卷 425-437页

作者： Magdalini Tsintou kyriakos Dalamagkas Nikos Makris Departments of Psychiatry and Neurology services Center for Neural Systems InvestigationsCenter for Morphometric AnalysisAthinoula A.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Psychiatry Psychiatry Neuroimaging LaboratoryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA University College of London Division of surgery&Interventional science Center for Nanotechnology&Regenerative MedicineUniversity College LondonLondonUK Department of Physical Medicine and Rehabilitation The University of Texas Health Science Center at HoustonHoustonTXUSA The Institute for Rehabilitation and Research Memorial Hermann Research Center The Institute for Rehabilitation and Research Memorial Hermann HospitalHoustonTXUSA Department of Anatomy&Neurobiology Boston University School of MedicineBostonMAUSA

The central nervous system is known to have limited regenerative *** only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such *** the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more *** and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system *** an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to *** review considers some regenerative therapies for central nervous system repair that hold promise for future clinical *** addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

关键词： animal models central nervous system regeneration clinical translation exosomes hydrogels neural tissue engineering nonhuman primates spinal cord injury stem cells stroke

An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice

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Hepatobiliary & Pancreatic Diseases International 2016年第2期15卷 220-222页

作者： Georgios Tziatzios Paraskevas Gkolfakis Ioannis s Papanikolaou George dimitriadis Konstantinos Triantafyllou Hepatogastroenterology Unit 2nd Department of Internal Medicine and Research Institute "Attikon" University General Hospital Medical School University of Athens

Despite the effectiveness of endoscopic retrograde cholangiopancreatography（ERCP） for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged postERCP jaundice due to toxicity of the contrast agent Iobitridol（~174;XENETIX, Guerbet, Roissy Cd G Cedex, France） in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/d L. Other potential causes of direct hyperbilirubinemia were ruled out and patient＇s liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.

关键词： endoscopic retrograde cholangiopancreatography jaundice adverse effect Iobitridol

Gut microbiota and non-alcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 572-581页

作者： Paraskevas Gkolfakis George dimitriadis Konstantinos Triantafyllou Hepatogastroenterology Unit Second Department of Internal Medicine and Research InstituteAttikon University General HospitalMedical SchoolAthens University

BACKGROUND： Non-alcoholic fatty liver disease （NAFLD） is a common disorder with poorly understood pathogenesis. Beyond environmental and genetic factors, cumulative data support the causative role of gut microbiota... 详细信息

关键词： non-alcoholic fatty liver disease non-alcoholic steatohepatitis gut microbiota 16s r RNA sequencing archaea

How random is the random forest ? Random forest algorithm on the service of structural imaging biomarkers for Alzheimer's disease: from Alzheimer's disease neuroimaging initiative(ADNI) database

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Neural Regeneration Research 2018年第6期13卷 962-970页

作者： stavros I.dimitriadis Dimitris Liparas Division of Psychological Medicine and Clinical Neurosciences School of Medicine Cardiff University Cardiff University Brain Research Imaging Centre School of Psychology Cardiff University school of Psychology Cardiff University Neuroinformatics Group Cardiff University Brain Research Imaging Centre School of Psychology Cardiff University Neuroscience and Mental Health Research Institute Cardiff University MRC Centre for Neuropsychiatric Genetics and Genomics School of Medicine Cardiff University High Performance Computing Center stuttgart (HLRs) University of Stuttgart Department of Informatics Aristotle University of Thessaloniki

Neuroinformatics is a fascinating research field that applies computational models and analytical tools to high dimensional experimental neuroscience data for a better understanding of how the brain functions or dysfunctions in brain diseases. Neuroinformaticians work in the intersection of neuroscience and informatics supporting the integration of various sub-disciplines（behavioural neuroscience, genetics, cognitive psychology, etc.） working on brain research. Neuroinformaticians are the pathway of information exchange between informaticians and clinicians for a better understanding of the outcome of computational models and the clinical interpretation of the analysis. Machine learning is one of the most significant computational developments in the last decade giving tools to neuroinformaticians and finally to radiologists and clinicians for an automatic and early diagnosis-prognosis of a brain disease. Random forest（RF） algorithm has been successfully applied to high-dimensional neuroimaging data for feature reduction and also has been applied to classify the clinical label of a subject using single or multi-modal neuroimaging datasets. Our aim was to review the studies where RF was applied to correctly predict the Alzheimer＇s disease（AD）, the conversion from mild cognitive impairment（MCI） and its robustness to overfitting, outliers and handling of non-linear data. Finally, we described our RF-based model that gave us the 1 ^（st） position in an international challenge for automated prediction of MCI from MRI data.

关键词： random forest Alzheimer's disease mild cognitive impairment neuroimaging classification machine learning biomarker magnetic resonance imaging

Advances in regenerative therapies for spinal cord injury:a biomaterials approach

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Neural Regeneration Research 2015年第5期10卷 726-742页

作者： Magdalini Tsintou kyriakos Dalamagkas Alexander Marcus seifalian UCL Centre for Nanotechnology & Regenerative Medicine Division of Surgery and Interventional ScienceUniversity College of London Royal Free London NHs Foundation Trust Hospital

spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mech- anism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing re- search interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaf- fold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerativel neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.

关键词： tissue engineering neuroregeneration repair central nervous system biomaterial regenerative medicine nanotechnology spinal cord injury

Is there a role for colon capsule endoscopy beyond colorectal cancer screening? A literature review

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World Journal of Gastroenterology 2014年第36期20卷 13006-13014页

作者： Konstantinos Triantafyllou Iosif Beintaris George D dimitriadis Hepatogastroenterology Unit Second Department of Internal Medicine and Research Institute Attikon University General Hospital Medical School Athens University 12462 Haidari Greece

Colon capsule endoscopy is recommended in Europe alternatively to colonoscopy for colorectal cancer screening in average risk individuals. The procedure has also been proposed to complete colon examination in cases of incomplete colonoscopy or when colonoscopy is contraindicated or refused by the patient. As tissue samples cannot be obtained with the current capsule device, colon capsule endoscopy has no place in diagnosing ulcerative colitis or in dysplasia surveillance. Nevertheless, data are accumulating regarding its feasibility to examine ulcerative colitis disease extent and to monitor disease activity and mucosal healing, even though reported results on the capsule’s performance in this field vary greatly. In this review we present the currently available evidence for the use of colon capsule endoscopy to complement colonoscopy failure to reach the cecum and its use to evaluate ulcerative colitis disease activity and extent. Moreover, we provide an outlook on issues requiring further investigation before the capsule becomes a mainstream alternative to colonoscopy in such cases.

关键词： Colon Capsule endoscopy Incomplete colonoscopy Ulcerative colitis Gastrointestinal endoscopy

Commentary on:“Human umbilical cord Wharton’s jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure”

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Asian Journal of Andrology 2022年第2期24卷 226-227页

作者： Fotios.dimitriadis Vasileios Palapelas Athanasios Zachariou Ioannis sokolakis Department of Urology Aristotle UniversitySchool of MedicineThessalonikiGreece 3^(rd)Department of Obstetrics and Gynecology Aristotle UniversitySchool of MedicineThessalonikiGreece Department of Urology Ioannina UniversitySchool of MedicineIoanninaGreece Department of Urology Martha-Maria Hospital NurembergNurembergGermany

The article by Wu et al.1 is an interesting and meticulous work investigating the role of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells(hWJ-MsCs)in the treatment of erectile dysfunction(ED)in th... 详细信息

关键词： diabetic al jelly

New endoscopes and add-on devices to improve colonoscopy performance

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World Journal of Gastroenterology 2017年第21期23卷 3784-3796页

作者： paraskevas gkolfakis georgios tziatzios george d dimitriadis konstantinos triantafyllou hepatogastro--enterology unit second department of internal medicine propaedeutic research institute and diabetes center medical school national and kapodistrian university of athens attikon university general hospital

Colonoscopy is the gold standard for colorectal cancer prevention; however, it is still an imperfect modality. Precancerous lesions can be lost during screening examinations, thus increasing the risk of interval cancer. A variety of factors either patient-, or endoscopist dependent or even the procedure itself may contribute to loss of lesions. sophisticated modalities including advanced technology endoscopes and add-on devices have been developed in an effort to eliminate colonoscopy's drawbacks and maximize its ability to detect potentially culprit polyps. Novel colonoscopes aim to widen the field of view. They incorporate more than one cameras enabling simultaneous image transmission. In that way the field of view can expand up to 330°. On the other hand a plethora of add-on devices attachable on the standard colonoscope promise to detect lesions in the proximal aspect of colonic folds either by offering a retrograde view of the lumen or by straightening the haustral folds during withdrawal. In this minireview we discuss how these recent advances affect colonoscopy performance by improving its quality indicators(cecal intubation rate, adenoma detection rate) and other metrics(polyp detection rate, adenomas per colonoscopy, polyp/adenoma miss rate) associated with examination's outcomes.

关键词： Colonoscopy Quality indicators Wide-angle view colonoscopes Add-on devices

The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

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Neural Regeneration Research 2021年第4期16卷 605-613页

作者： Magdalini Tsintou kyriakos Dalamagkas Tara LMoore Yogesh Rathi Marek Kubicki Douglas LRosene Nikos Makris Departments of Psychiatry and Neurology services Center for Neural Systems InvestigationsCenter for Morphometric AnalysisAthinoula A.Martinos Center for Biomedical ImagingMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Psychiatry Psychiatry Neuroimaging LaboratoryBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA University College of London Division of surgery&Interventional science Center for Nanotechnology&Regenerative MedicineUniversity College LondonLondonUK Department of Physical Medicine and Rehabilitation The University of Texas Health Science Center at HoustonHoustonTXUSA The Institute for Rehabilitation and Research Memorial Hermann Research Center The Institute for Rehabilitation and Research Memorial Hermann HospitalHoustonTXUSA Department of Anatomy&Neurobiology Boston University School of MedicineBostonMAUSA

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNs)*** is known that the CNs demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNs therapeutics *** the high prevalence of CNs conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury *** vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell *** the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative *** review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable *** rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the *** sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration ***,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of m

关键词： cortical injury exosomes extracellular vesicles hydrogels neural tissue engineering neural tissue repair neuroregeneration non-human primates stroke