Stem cell engineering

Field of Interest

The overall goal of the laboratory is to combine engineering principles with basic biological science to rationally understand the mechanisms governing cell behavior. The research of the lab addresses fundamental and practical problems in the areas of stem cell engineering, cell therapy and development of in vitro models for functional healthy and diseased tissues.
We design and develop innovative technologies for the spatial-temporal control of stem cell culture at the micro-environmental scale. We are currently working on: methods of micro-fabrication; micro- and macro-bioreactor design; molecular cell biology; computational biology; microscopic mass transport modeling

In vitro model

Skeletal and cardiac muscle play essential roles for the life of an organism but these complex tissues may be affected by a variety of pathologies which are in many cases invalidating or, in the worst case scenario, lethal. The elucidation of the intricate three dimensional structure-function relationship of skeletal and cardiac muscle tissues is certainly a critical issue for a deeper understanding of the patho-physiological processes in which they are involved. In this context, we are focused on the development of in vitro models of human skeletal and cardiac muscle simulating the particular spatial arrangement of cells and extracellular matrix proteins, peculiar of their structure and function in vivo. Spatial distribution of the cells is obtained by the deposition of proteins by the microcontact printing technique.
In vitro models could potentially represent a complementary tool bridging the gap between conventional cell culture, animal models and patients in the process of drugs or therapies development.
Our research holds the potential to develop an in vitro model of human dystrophic skeletal muscle suitable for screenings and development of therapy and for the investigation of relevant molecular and biological mechanisms in a highthroughput fashion.

In vitro cardiac model

Cell transplantation is a promising approach to replace scarred or nonfunctional myocardium in a diseased heart. At the moment the major limitations concern the production of the required amount of functional cardiomyocytes for clinical applications (due to the limited availability and proliferative capacity of these cells, especially in the case of an infarcted hearth), and the low functional engraftment of the transplanted cells in an environment characterized by oxidative stress, inflammatory cytokines and fibrous scar tissue.
In order to obtain an adequate number of cells for clinical applications, we culture human embryonic stem cells onto microstructured photo-polymerizable poly-acrylamide hydrogels coupled to micro-liter bioreactors to enhance cell proliferation and promote the differentiation towards the cardiac lineage. These technologies and the small volumes involved permit to simultaneously test a wide range of cell culture conditions thus representing an invaluable tool in moving from small to large scale cultivation of cells for clinical applications and drug screening.
Beside studying physiological conditions for stem cell differentiation into cardiomyocytes, we aim at studying the effects of the major pathological stimuli of an infarcted myocardium on human cardiomyocytes viability and functional properties. In this sight, we aim at realizing an in vitro model of infracted hearth, based on microstructured culture of human cardiomyocytes coupled with a microfluidic platform which allows the multi-parametric spatial-temporal simulation of the in vitro pathological environment.

In vitro skeletal muscle model

Duchenne Muscular Dystrophy is the most common, lethal, inherited disease of skeletal and cardiac muscles. Although several years have passed since the identification of the molecular defect involved in the Duchenne Dystrophy, long term therapies have not been developed yet. Our research efforts are aimed at producing in vitro human skeletal muscle myotubes exhibiting functional properties by a proper design of the in vitro artificial niche.
We aim at integrating tissue engineering tools and biological skills in order to reproduce the dominant physiological stimuli that guide myofiber formation in vivo; in particular, we culture dystrophic myoblasts onto an hydrogel with mechanical properties resembling those of muscular tissue in vivo. Spatial alignment of the myoblasts is obtained by the the microcontact printing technique and electrical stimulation is coupled to the culture in order to mimic the physiological electrical signals of muscle tissue and study their functional activity.

Cell therapy

Cell therapy represents an appealing solution for the treatment of diseased muscle or the reconstruction of muscle after severe injury. The success of innovative therapeutic strategies depend on the development of suitable technologies to engineer myogenic cells and biocompatible scaffolds.
In this perspective, we developed an injectable, biocompatible and biodegradable photo-polymerizable hydrogel able to maintain cell myogenic potential and capable of being delivered through minimally invasive techniques. To further improve the efficiency of cell delivery, we aim at developing injectable biomaterials functionalized with extracellular matrix proteins and with tunable growth factors release rates.

Synoptic CV

Selected VIMM Publications

• Serena E, Figallo E, Tandon N, Cannizzaro C, Gerecht S, Elvassore N, Vunjak-Novakovic G (2009) Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Exp. Cell Res. 315:3611-9.
• Serena E, Figallo E, Tandon N, Cannizzaro C, Gerecht S, Elvassore N, Vunjak-Novakovic G (2009) Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Exp. Cell Res. 315:3611-9.
• Flaibani M, Boldrin L, Cimetta E, Piccoli M, De Coppi P, Elvassore N (2009) Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. 15:2447-57.
• Flaibani M, Boldrin L, Cimetta E, Piccoli M, De Coppi P, Elvassore N (2009) Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. 15:2447-57.

VIMM Publications

• Serena E, Figallo E, Tandon N, Cannizzaro C, Gerecht S, Elvassore N, Vunjak-Novakovic G (2009) Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Exp. Cell Res. 315:3611-9.
• Serena E, Figallo E, Tandon N, Cannizzaro C, Gerecht S, Elvassore N, Vunjak-Novakovic G (2009) Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Exp. Cell Res. 315:3611-9.
• Flaibani M, Boldrin L, Cimetta E, Piccoli M, De Coppi P, Elvassore N (2009) Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. 15:2447-57.
• Flaibani M, Boldrin L, Cimetta E, Piccoli M, De Coppi P, Elvassore N (2009) Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. 15:2447-57.

Additional Publications

• Cimetta E, Pizzato S, Bollini S, Serena E, De Coppi P, Elvassore N (2009) Production of arrays of cardiac and skeletal muscle myofibers by micropatterning techniques on a soft substrate. 11:389-400.
• Cimetta E, Figallo E, Cannizzaro C, Elvassore N, Vunjak-Novakovic G (2009) Micro-bioreactor arrays for controlling cellular environments: design principles for human embryonic stem cell applications. Methods 47:81-9.
• Serena E, Flaibani M, Carnio S, Boldrin L, Vitiello L, De Coppi P, Elvassore N (2008) Electrophysiologic stimulation improves myogenic potential of muscle precursor cells grown in a 3D collagen scaffold. Neurol. Res. 30:207-14.
• Cannizzaro C, Tandon N, Figallo E, Park H, Gerecht S, Radisic M, Elvassore N, Vunjak-Novakovic G (2007) Practical aspects of cardiac tissue engineering with electrical stimulation. Methods Mol. Med. 140:291-307.
• Callegari A, Bollini S, Iop L, Chiavegato A, Torregrossa G, Pozzobon M, Gerosa G, De Coppi P, Elvassore N, Sartore S (2007) Neovascularization induced by porous collagen scaffold implanted on intact and cryoinjured rat hearts. Biomaterials 28:5449-61.
• Cimetta E, Flaibani M, Mella M, Serena E, Boldrin L, De Coppi P, Elvassore N (2007) Enhancement of viability of muscle precursor cells on 3D scaffold in a perfusion bioreactor. Int J Artif Organs 30:415-28.
• Figallo E, Cannizzaro C, Gerecht S, Burdick JA, Langer R, Elvassore N, Vunjak-Novakovic G (2007) Micro-bioreactor array for controlling cellular microenvironments. 7:710-9.
• Figallo E, Flaibani M, Zavan B, Abatangelo G, Elvassore N (0) Micropatterned biopolymer 3D scaffold for static and dynamic culture of human fibroblasts. Biotechnol. Prog. 23:210-6.

Selected Seminars

Contact

Nicola Elvassore Venetian Institute of Molecular Medicine Via Orus 2 35129 Padua — Italy

Last updated: 28/03/2010, NE ·