Human in vitro models could represent a complementary tool bridging the gap between conventional cell culture, animal models and patients in the process of drug and therapy development. Our research holds the potential to develop in vitro models based on human artificial tissues for screening therapies and for the investigation of relevant molecular and biological mechanisms in a high-throughput fashion.

Micro-scale cell reprogramming

The choice of a good cell source is key for both regenerative medicine and laboratory model development. The possibility of reprogramming human adult somatic cells to an embryonic-like state, called induced pluripotent stem cells (iPS) has been recently discovered and offers breakthrough perspectives for research and clinical applications, including modeling of human development, associated congenital diseases, familiar predisposition, drug efficacy and safety screening. In this scenario, we have developed robust and efficient technology able to control and enhance the effectiveness of the reprogramming process.

ReprogrammingReprogramming on chip.

Cell differentiation on chip

We focus on the development of in vitro models of human tissues (skeletal and cardiac muscles, and liver) biomimicking the specific spatial arrangement of cells and extracellular matrix proteins, peculiar of their structure and function in vivo. Spatial control of the cells and substrate chemical and mechanical properties are obtained by micro-fabrication technologies and substrate engineering.

In this sight, we are realizing an in vitro model of hearth tissue, based on micro-structured cultures of human cardiomyocytes coupled with a microfluidic platform which allows the multi-parametric spatio-temporal simulation of the in vitro pathological environment.

Calcium transients in a human cardiomyocyte array.

We integrate tissue engineering tools and biological skills in order to reproduce the dominant physiological stimuli that guide myofiber formation in vivo; in particular, we culture myoblasts on a hydrogel with mechanical properties resembling those of muscular tissue in vivo. Spatial alignment of the myoblasts is obtained by the micro-contact printing technique, and electrical stimulation is coupled to the cultures in order to mimic the physiological electrical signals of muscle tissue in order to study skeletal muscle functional activity.

myotubesHuman myotubes in microfluidics.

The shortage of hepatocytes for clinical applications, in alternative to liver transplantation, causes a vast interest in pluripotent stem cells as a source for human hepatocytes. To obtain mature hepatic cells through differentiation, there is a need to better mimic the in vivo microenvironment. We developed a microfluidic culture system able to generate a stable oxygen concentration gradient for long-term cultures mimicking the in vivo hepatic lobule microenvironment. This system is easily coupled with standard assays for detection of hepatocyte functionality.

HepatocytesHuman hepatocytes.

Contact

Office: +39-049-827-5469
Lab (DII): +39-049-827-5467
Lab (VIMM): +39-049-7923-219
Fax: +39-049-827-5461
nicola.elvassore@unipd.it

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