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Mesenchymal stem cell secretome and extracellular vesicles for neurodegenerative diseases: Risk-benefit profile and next steps for the market access

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Bioactive Materials 2023年第11期29卷 16-35页

作者： Lorella Giovannelli elia Bari Claudio Jommi Fulvio Tartara daniele Armocida Diego Garbossa Fabio Cofano Maria Luisa Torre Lorena Segale Department of Pharmaceutical Sciences University of Piemonte Orientale28100NovaraItaly IRCCS Mondino Foundation 27100PaviaItaly A.U.O Policlinico Umberto INeurosurgery DivisionHuman Neurosciences DepartmentSapienza University00135RomaItaly Department of Neuroscience Rita Levi Montalcini Neurosurgery UnitUniversity of Turin10126TurinItaly PharmaExceed S.r.l 27100PaviaItaly

Neurodegenerative diseases represent a growing burden on healthcare systems worldwide. Mesenchymal stem cells (MSCs) have shown promise as a potential therapy due to their neuroregenerative, neuroprotective, and immunomodulatory properties, which are, however, linked to the bioactive substances they release, collectively known as secretome. This paper provides an overview of the most recent research on the safety and efficacy of MSC-derived secretome and extracellular vesicles (EVs) in clinical (if available) and preclinical models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington’s disease, acute ischemic stroke, and spinal cord injury. The article explores the biologically active substances within MSC-secretome/EVs, the mechanisms responsible for the observed therapeutic effects, and the strategies that may be used to optimize MSC-secretome/EVs production based on specific therapeutic needs. The review concludes with a critical discussion of current clinical trials and a perspective on potential future directions in translating MSC-secretome and EVs into the clinic, specifically regarding how to address the challenges associated with their pharmaceutical manufacturing, including scalability, batch-to-batch consistency, adherence to Good Manufacturing Practices (GMP) guidelines, formulation, and storage, along with quality controls, access to the market and relative costs, value for money and impact on total expenditure.

关键词： Exosomes Microvesicles Secretome Mesenchymal stem cells Secretome formulation Brain regeneration

InAs nanowire superconducting tunnel junctions： Quasiparticle spectroscopy, thermometry, and nanorefrigeration

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Nano Research 2017年第10期10卷 3468-3475页

作者： Jaakko Mastomaki Stefano Roddaro Mirko Rocci Valentina Zannier daniele Ercolani Lucia Sorba Ilari J. Maasilta Nadia Ligato Antonio Fornieri elia Strambini Francesco Giazotto NEST Scuola Normale Superiore and Istituto Nanoscienze-CNR Piazza S. Silvestro 12 I-55127 Pisa Italy Nanoscience Center Department of Physics University of Jyvaskyla 40014 Jyvaskyla Finland

We demonstrate an original method based on controlled oxidation for creating high-quality tunnel junctions between superconducting A1 reservoirs and InAs semiconductor nanowires （NWs）. We show clean tunnel characteristics with a current suppression by 〉4 orders of magnitude for a junction bias well below the A1 gap of △0≈ 200 μeV. The experimental data agree well with the Bardeen- Cooper-Schrieffer theoretical expectations for a superconducting tunnel junction. The studied devices employ small-scale tunnel contacts functioning as thermometers as well as larger electrodes that provide proof-of-principle active cooling of the electron distribution in the NWs. A peak refrigeration of approximately δT = 10 mK is achieved at a bath temperature of Tbath≈ 250-350 mK for our prototype devices. This method introduces important perspectives for the investigation of the thermoelectric effects in semiconductor nanostructures and for nanoscale refrigeration.

关键词： InAs nanowire superconducting tunnel junction thermometry nanorefrigeration

Antitachycardia pacing programming in implantable cardioverter defibrillator:A systematic review

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World Journal of Cardiology 2017年第5期9卷 429-436页

作者： elia De Maria daniele Giacopelli Ambra Borghi Letizia Modonesi Stefano Cappelli Cardiology Unit Ramazzini Hospital Biotronik Italia Dipartimento Clinico

Implantable cardioverter defibrillator(ICD) programminginvolves several parameters. In recent years antitachycardia pacing(ATP) has gained an increasing importance in the treatment of ventricular arrhythmias, whether slow or fast. It reduces the number of unnecessary and inappropriate shocks and improves both patient's quality of life and device longevity. There is no clear indication regarding the type of ATP to be used, except for the treatment of fast ventricular tachycardias(188 bpm-250 bpm) where it has been shown a greater efficacy and safety of burst compared to ramp; 8 impulses in each sequence of ATP appears to be the best programming option in this setting. Beyond ATP use, excellent clinical results were obtained with programming standardization following these principles: extended detection time in ventricular fibrillation(VF) zone; supraventricular discrimination criteria up to 200 bpm; first shock in VF zone at the maximum energy in order to reduce the risk of multiple shocks. The MADIT-RIT trial and some observational registries have also recently demonstrated that programming with a widespread use of ATP, higher cut-off rates or delayed intervention reduces the number of inappropriate and unnecessary therapies and improves the survival of patients during mid-term follow-up.

关键词： Implantable cardioverter defibrillator programming Antitachycardia pacing Ventricular tachycardia Electrical antitachycardia therapy

Video Analysis of Side Hop Technique in Trials

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Journal of Sports Science 2017年第1期5卷 58-63页

作者： Rodolfo Vastola Silvia Coppola Albano daniele Francesca D'elia Motion Analysis Laboratory Department of Human Philosophical and Educational Sciences University of Salerno Fisciano Salerno 84084 ltaly

Trials is a specialty of off-road cycling in which the rider has to face obstacle courses without resting feet on the ground. Technique in this sport has a great importance, since it reduces the risk of committing penalties and allows more efficient execution of the gesture. To improve technique, the motion analysis allows to study the gesture both qualitatively and quantitatively. In this work video analysis was used to study the side hop from rear wheel technique. Two different executions of this technique were analyzed. The primary purpose is the identification of the phases that make up the technical gesture. It was given an explanation to the movement strategies adopted in the execution of the jump in the two different situations.

关键词： Bike trials cycling vertical jump video analysis sport technique

Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer

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World Journal of Obstetrics and Gynecology 2013年第4期2卷 167-175页

作者： Marco Lotti Luisa Maria Busci Luca Campanati Fausto Catena Federico Coccolini Naoual Bakrin Pierandrea De Iaco Giorgio Ercolani Giuseppe Grosso Michele Pisano elia Poiasina Diego Rossetti Martina Rossi Claudio Zamagni Paolo Bertoli Antonio daniele Pinna Luigi Frigerio Luca Ansaloni Unit of General Surgery 1 Papa Giovanni XXIII Hospital 24128 Bergamo Italy Unit of Gynecology and Obstetrics Papa Giovanni XXIII Hospital 24128 Bergamo Italy Unit of General Surgery St.Orsola-Malpighi University Hospital 40138 Bologna Italy Department of Gynecology Lyon Sud Hospital69310 Pierre Benite France Unit of Gynecology and Obstetrics St.Orsola-Malpighi University Hospital V40138 Bologna Italy Medical Oncology St.Orsola-Malpighi University Hospital 40138 Bologna Italy

AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage ⅢC-Ⅳ epithelial ovarian cancer(EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modifi ed Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy(ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.

关键词：辅助化疗治疗方法临床分析腹腔镜