StemFunc
Biomimetic Active Environment for Maturing and Differentiating Stem Cells
Principal Investigators at ASE: Prof. Jukka Lekkala and Prof. Pasi Kallio
Duration of the project: 2008 – 2011
Project description:
The main objective of the project is to develop novel methods to produce transplantable functional neuronal cells and cardiomyocytes from stem cells. Those cells are urgently needed to treat neurological disorders, traumas and cardiac failure in humans. Hence, new approaches to produce functional cells are needed. Our aim is to investigate and assemble biomimetic cell culture environments for culturing these cells.
ASE / MST develops an automatic environment which facilitates cell cultivation and active stimulation of the cells. Our approach is to develop a multifunctional modular microfluidic platform which at the same time guides the cell growth, changes the medium, facilitates drug inducement and provides gas supply. We have already demonstrated that activity of neuronal cells can be enhanced in our polydimethylsiloxane based structures and determined the appropriate flow rates (using CFD simulations and PIV measurements) to avoid unwanted differentiation due to shear forces.
ASE / MST also develops technologies for mechanical stimulation of cardiac cells using controlled stretching of the cultivation membrane.
Figure 1: A) Cell cultivation chamber for long-term cell cultures composed of a perfusion module and a connection module. B) Perfusion module implemented on a MEA plate.
Figure 2: Time-average fluid velocity vector fields at the cell chamber inlet with the flow rate of 1 µl/min and the inlet step height of 470 µm. A) µPIV measurement and B) 3D-CFD simulation.
Funding:
The Academy of Finland
Partners:
• Professor Jari Hyttinen and Minna Kellomäki in the Department of Biomedical Engineering at Tampere University of Technology and
• Group Leaders Heli Skottman, Katriina Aalto-Setälä and Susanna Narkilahti in the Regea Institute of Biomedical Technology at the University of Tampere.
Personnel at ASE/MST:
• MSc Joose Kreutzer,
• BSc Feihu Zhao
Publications:
• Kreutzer, J., Honkanen, M., Laaksonen, J. & Kallio, P. ”Perfusion Characterization using Flow Simulations and µPIV Measurements”. Proceedings of the 2nd European Conference on Microfluidics - Microfluidics 2010, Toulouse, France, December, 2010.
• Kreutzer, J., Lappalainen, R., Ylä-Outinen, L., Narkilahti, S., Mikkonen, J.E., & Kallio, P. “Laminin Coated PDMS Surfaces for Long-Term MEA Measurements of hESC-Derived Neural Networks”. Proceedings of Symposium on Microelectrode Arrays in Tissue Engineering (MEATE 2009). Tampere, Finland, June 2009.
• Ikonen, L., Kreutzer, J., Hyttinen, J., Kallio, P., Kerkelä, E. and Aalto-Setälä, K., ”Mechanical Stimulus and Growth of Cardiomyocytes on Biomaterials”, Tissue Engineering and Regenerative Medicine International Society”, Galway, Ireland, June 2010.
• Ikonen L., Kreutzer J., Hyttinen J., Kallio P., Kerkelä E. & Aalto-Setälä K., “Mechanical Stimulus and Growth of Cardiomyocytes on Biomaterials”, 22nd European Conference on Biomaterials, Lausanne, Switzerland, September 2009.
• Lehtonen L., Kreutzer J., Hyttinen J., Kallio P., Kerkelä E. & Aalto-Setälä K., “Coating of the PDMS for Mechanical Stimulation of Cardiomyocytes”, 6th Tissue Engineering Symposium, Tampere, Finland, June 2009.
Personnel at ASE / Sensor Technology and Biomeasurements group:
Project description:
Microelectrode arrays (MEAs) are used for field potential measurements and electrical stimulation of cells. Different biological research questions set different requirements for microelectrode sizes and locations and if cell growth guiding structures and coatings area applied on MEAs or some sensors are integrated on MEAs, also the basic MEA structure must be customized to ensure compatibility with the fabrication processes of those additional features. The all-titanium MEA technology developed in this project by the ASE Sensor Technology and Biomeasurements group offers a cost effective way to fabricate custom MEAs, whose performance is comparable to commercial MEAs.
In order to monitor cell growth conditions, both pH and oxygen levels of the cell culturing medium are good indicators. To find microsized, biocompatible and long term stable concept for pH sensing, several approaches have been studied by the ASE Sensors and Biomeasurements group. Glass capillary electrodes and planar ALD iridium oxide based electrodes have been the most promising candidates so far and the same approaches will be studied also related to oxygen sensing.
Continuation:
Several Academy of Finland, Tekes and personal grant applications have been submitted or are under preparation to enable the continuation of the multidisciplinary co-operation also in the future.
Personnel:
•MSc Tomi Ryynänen
•MSc Kirsi Nurminen
Publications:
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Ryynänen, T., Kujala, V., Ylä-Outinen, L., Korhonen, I., Tanskanen, J., Kauppinen, P., Aalto-Setälä, K., Hyttinen, J., Kerkelä, E., Narkilahti, S., Lekkala, J., 2011. All-Titanium Microelectrode Array for Field Potential Measurements from Neurons and Cardiomyocytes – a Feasibility Study. Micromachines 2011, 2(4), 394-409.
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Ryynänen, T., Nurminen, K., Hämäläinen, J., Leskelä, M., Lekkala, J., 2010. pH electrode based on ALD deposited iridium oxide. Eurosensors XXIV, 5.-8.9.2010, Linz, Austria.
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Nurminen, K., Ylä-Outinen, L.. Narkilahti, S., Lekkala, J., 2010. A Capillary pH Electrode for Evaluating Long Term Culturing of Neural Cell Populations. Eurosensors XXIV, 5.-8.9.2010, Linz, Austria.
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Ryynänen, T., Kujala, V., Ylä-Outinen, L., Kerkelä, E., Narkilahti, S., Lekkala, J., 2010. Polystyrene coated MEA. 7th International Meeting on Substrate-Integrated Microelectrode Arrays, 29.6.-2.7.2010, Reutlingen, Germany.
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Nurminen, K., 2009. Master of Science thesis, Tampere University of Technology, 90 pp.
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Ryynänen, T., Kattipparambil Rajan, D., Lekkala, J., 2009. Concept for low-cost rapid prototyping of new MEA designs. Symposium on Microelectrode Arrays in Tissue Engineering (MEATE 2009) June 4-5 2009, Tampere, Finland.
Links: www.tut.fi/bme/stemfunc
