seminari ifc1

Il nuovo appuntamento per i Seminari IFC è giovedì 2 Aprile 2015, alle ore 15, presso l’Aula 27 ed. A dell’Area della Ricerca del CNR, Via G. Moruzzi 1, Pisa con:

  • Prof. Gianluca Ciardelli - DIMEAS - Dipartimento di Ingegneria Meccanica e Aerospaziale, Politecnico di Torino “MIND - Engineering physiologically and pathologically relevant organ Models for the INvestigation of age related Diseases”

  • Dr.ssa Susanna Sartori - DIMEAS - Dipartimento di Ingegneria Meccanica e Aerospaziale, Politecnico di Torino "A paradigm shift from tissue engineering to organ models: the cardiac tissue as case study”

  • Dr. Federico Vozzi - Istituto di Fisiologia Clinica, Area CNR Pisa  “Bioengineering approach  to an in-vitro model of cardiac aging” 

  • Dr. Gianfranco Politano - DAUIN - Dipartimento di Automatica e Informatica, Politecnico di Torino "System biology modelling in senescence and aging"

 

Di seguito le presentazioni dei relatori e un sommario delle relazioni (in inglese)

 

 

The MIND Project: Engineering physiologically and pathologically relevant organ Models for the INvestigation of age related Diseases

Gianluca Ciardelli has a PhD in Natural Sciences from the Swiss Federal Institute of Technology (ETH-Zurich) and is currently a full-time Professor in Bionanotechnology at Politecnico di Torino. He is coordinating a group of 15 people on average carrying out research in the development of biomedical polymers and the realization of scaffolds for tissue engineering, drug delivery in nanomedicine, and molecular recognition. He is the author of over 110 peer reviewed international papers, 9 book chapters and 12 patents; the h-index is 25. The highest impacting journals where the papers were published are a.o. Biomacromolecules, Acta Biomaterialia,Anal. Chim. Acta, and Macromol. Biosci.

As a result of decreasing mortality and birth rates in Europe, the expense of caring for the aging population places an ever increasing burden on national economies. It is every human being's right to live with dignity and the absence of suffering throughout his/her lifespan, but our lack of knowledge on systemic, organ, tissue and cell degeneration due to senescence do mean that the aging process it is often beyond our control. Aging however is not just a process occurring in single cells, but is also associated with changes in the physiological microenvironment and alterations in signaling between cells and even distant tissues and organs, leading to systemic age related diseases such as osteoporosis, cardiovascular dysfunction and cognitive impairments. The MIND project aims at overcoming the current lack of models for the study of the physiological conditions associated with aging through the development –by advanced bioengineering technologies- of in vitro dynamic models, able to reproduce the physio-pathological conditions of aged tissues, while respecting the 3 Rs ("Replacement, Refinement, Reduction") principle of animal testing.

The multidisciplinary consortium, composed mainly of bioengineers, flanked by clinicians, biologists, experts in the regulatory aspects of health and physical and electronic engineers, will pool its varied expertise and knowledge to design, realize, model and characterize new systems for the investigation of ageing and age related diseases, with reference to four tissues which are particularly compromised by age related degeneration: cardiac, bone, epithelial and neural tissue.

The project represents a first step towards the long-term goal of generating reliable biomimetic models of tissues for the study of pathological conditions and the development of pharmacological strategies, reducing animal and clinical testing, as well as the time and costs associated with them.

Applying tissue engineering principles to develop organ models: the human heart as a case study

Susanna Sartori is a laboratory technician at Politecnico di Torino. She received a Master's degree in Chemistry from the University of Pisa. Her research interests cover polymers as biomaterials for tissue engineering and controlled drug delivery with a special focus on polyurethane materials, mainly for cardiac applications. She has co-authored 19 peer-reviewed publications and book chapters and one patent. She is also a co-founder of Geltis, a spin-off of Politecnico di Torino focusing on polyurethane sol-gel systems for biomedical applications.

The average lifespan of humans is increasing, and with it the percentage of old people is growing rapidly. Within elderly people, cardiovascular disease is the leading cause of death, and the cost associated with treatment will continue to increase. The mechanism by which heart function declines becoming increasingly exposed to diseases, in association with age, is still not clear. Engineered tissue models offer new options to cover this lack of knowledge, allowing a better understanding of disease progress and the development of new treatments.

In this talk biomimetic polyurethane scaffolds are proposed as myocardial models. In order to resemble the heart tissue mechanical properties, young and aged artificial tissues were produced by a selected polyurethane (PUR), and a polyurethane-polycaprolactone blend respectively. The PUR was chosen because it shows an elastomeric-like behavior, similar to muscle tissues. The polymer blends were studied in order to simulate the aged muscle, which is stiffer compare to the young one, contributing to the decrease in compliance of the left ventricular wall. Polymer scaffolds were produced by Thermal Induce Phase Separation, to obtain oriented fibers texture like the cardiac tissues. Scaffolds were further surface functionalized with fibronectin, which is one of the main Extracellular Matrix components and is known to promote myocardial cells proliferation and regulate cell function during tissue repair.

Bioengineering approach to an in-vitro model of cardiac aging

Federico Vozzi is a researcher of Institute of Clinical Physiology. He has a Ph.D. in Drugs Science of Faculty of Pharmacy (University of Pisa). His research interests are focused on the study of biomaterials for Cardiac and Soft Tissue Engineering applications, the development of Dynamic Cell Culture Systems and the Virtual Physiology Human models of cardiovascular diseases. He is author of 24 peer-reviewed publications and 3 patents.

In elderly people a series of cardiac disorders can occur such as: increased mass of the left ventricle, decrease in the ability to increase cardiac output in response to stress and more frequent ischemic heart disease. In comparison with young people, increased heart rate, maximum cardiac output, maximum oxygen consumption, and vascular dilation in response to adrenergic stimulation or endothelium-released vasodilators are achieved sooner. Because of the huge complexity of the in-vivo environment, systematic study of phenomena of cellular response to mechanical stimulation has relied heavily on the use of in-vitro preparations. Cardiac tissue engineering approaches have a relevant role in this type of study focusing the attention on the production of support for cell growth with biomechanical and biochemical characteristics similar to those of cardiac muscle. In the same time, it is important to recovery not only the tissue structure but also to insert these constructs in a dynamic environment to replicate the physiological living conditions.

In this talk a cardiac cell growth support (PUR scaffold) stimulated by a controlled hydrostatic pressure delivery system (SQPR, SQueeze PRessure bioreactor) is presented. The biological properties of PUR scaffolds are studied trough the use of rat cardiomyocytes. A biological characterization is performed in terms of several molecular biology markers, immunohistochemistry and electrophysiological properties, both in static and in dynamic environmental conditions. This last part has been obtained in SQPR system, able to generate mechanical stimuli on cells with help of hydrostatic pressure. Hydrostatic compression holds several substantial attractions: simplicity of the equipment, spatial homogeneity of the stimulus, ease of configuring multiple loading replicates as also of delivering and transducing either static or transient loading inputs.

The use 3D cell system cultured in a dynamic environment (respect to static culture) helps to recreate more physiological cell life conditions, furnishing a new model for the study of aging.

System biology modelling in senescence and aging

Gianfranco Politano has a MS and a PhD in Computer Engineering from the Politecnico di Torino (Italy). He is currently a Post-DOC Research Fellow in Bioinformatics at Politecnico di Torino. He authored 27 peer reviewed international papers. Gianfranco Politano is member of IEEE and Computer Society; he serves in the IEEE/CS Digital Library Operations Committee and IEEE/TC Technical Committee on Computational Life Sciences. He is also member of the Scientific Committee of Museo Regionale di Scienze Naturali di Torino (Regional Museum of Natural Sciences). Gianfranco Politano is adjuncted professor at Università degli Studi di Torino (Italy) and Turin-Tashkent Polytechnic University (Uzbekistan).

Current research activities mainly focus on the analysis of gene regulatory networks (GRNs), with particular emphasis on post-transcriptional regulatory motif analysis, and topological analysis of GRNs.

A biological network (BN) is a model able to describe the set of interactions that influence genetic expression in a well-defined biological process. BN are general models, whose nodes can represent different types of interactors (genes, microRNA, proteins, transcription factors, ecc.), and edges can describe different types of reaction (inhibition, activation, microRNA co-transcriptions, ecc).

In last decades a huge effort was dedicated to annotate the major number of biological processes. Nowadays, are available several online database containing genetic regulation BN (usually composed by only genes), grouped considering the process that they describe. It is important to consider that each BN available in public database is an abstraction respect to the real cell behavior, in a cell, in fact, the interactors holistically regulate each other, whereas BNs are atomic sub-network often completely disjointed to each other.

The work in PRIN project is focused to functionally model the regulatory phenomena involved in senescence and aging. A model was developed able to: i) minimize the actual BN compartmentalization, integrating multiple BN, and, ii) enrich the holistic model by integrating information related to transcription factors and microRNA regulations. The resulting model highlights the most important regulatory elements in the aging biological process. The resulting model was analyzed and refined with well-established System Biology methodologies in order to show a small set of genes, along with their related set of complex cross-regulations. In order to asses the overall reliability of the proposed model, the gene set will be further validated with biological experimentations.