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Article

Heart beats on a multiwell plate

13.6.2018

Launched in early 2018, the Centre of Excellence in Body-on-Chip Research is funded by the Academy of Finland and coordinated by Tampere University of Technology (TUT). The centre has an ambitious goal to build body-on-chip platform that mimics the functions of the human body and, for example, provides an unprecedented level of detail into the therapeutic mechanisms of drugs.

“Our goal is to develop a novel body-on-chip platform that resembles a simplified version of the human body. The platform will combine multiple lab-grown cell types that are differentiated from stem cells, such as heart, brain and liver cells,” says Professor Pasi Kallio of TUT, whom we meet while filming a video of the Centre of Excellence (CoE).

The body-on-chip platform will consist of cultured tissue blocks complete with vascular and nervous systems.

“The platform will enable us to investigate and analyse a broad range of biological processes occurring in the human body and, for example, identify drugs that work best for each patient. The findings will also hold promise for the development of new drugs,” continues Kallio.

With funding secured until 2025, the CoE continues the long history of successful collaboration between TUT and the University of Tampere (UTA). The two universities have previously collaborated, among other things, to develop human spare parts.

Gloves on before filming

The body-on-chip concept becomes clearer when we visit the CoE’s facilities and meet the researchers while filming our video. Mari Pekkanen-Mattila, postdoctoral researcher in the Institute of Biosciences and Medical Technology (BioMediTech) that is jointly administered by TUT and UTA, gives us a tour of the laboratories. She coordinates the CoE.

“Our researchers who are based at TUT develop the technologies that are used for research purposes at BioMediTech and conduct research on related equipment and materials. Cells are mainly cultured in our newly renovated state-of-the-art facilities here in the Arvo building on the UTA campus,” says Pekkanen-Mattila.

Valtteri Kamppinen and Valtteri Pönkkä, who are filming the CoE video as part of their thesis at Tampere Vocational College Tredu, keep a lookout for ideal filming locations as they go. The site differs from their earlier video projects in many ways. For example, before entering the Heart Lab they must don appropriate protective clothing: a lab coat, shoes, a purple paper hat and rubber gloves.

“This is something I’ve never done before: handling a camera while wearing rubber gloves. And I certainly won’t get cold with all this on,” laughs Valtteri Pönkkä, who is in charge of filming.

WHAT? Centre of Excellence in Body-on-Chip Research

  • Holds the Academy of Finland's Centre of Excellence status from 2018 to 2025
  • Centres of Excellence represent the highest calibre of research in their field
  • Joint project between TUT and the University of Tampere
  • Multidisciplinary and international community of scientists
  • Headed by Professor Minna Kellomäki
  • The goal is to develop a unique body-on-chip platform for modelling the human body
  • Spread across two campuses in Hervanta and Kauppi
  • Approximately 100 researchers and students
 

Mari Pekkanen-Mattila routinely takes a shallow plastic box from an incubator that looks like a refrigerator.

“We grow heart cells on these multiwell plates. The differentiated cells form clusters that are then mechanically and enzymatically disassociated into single cells,” she explains.

Tiny white flecks can be seen floating in a pink liquid in the shallow wells of the plate.

“Oh, these appear to be too young to be beating. Heart cells start beating when they are about 10-12 days old,” says Pekkanen-Mattila and changes the slide of her microscope.

A screen next to the microscope shows that the individual heart cells growing on the plate are indeed beating. The team of researchers employs the same method to study, for example, brain, nerve and liver cells. When the cells are eventually organised into tissues connected with vascular and nervous systems, a human body in vitro (literally meaning ‘in a glass’) will begin to take shape.

Glowing nuclei under a microscope

Extremely detailed data on cells is required in order for the researchers to develop a functional body-on-chip and uncover the mechanisms whereby the body-on-chip and the materials under review affect cells and their behaviour. The PCR machine in the next room is used to analyse the gene expression of different cells.

“We can determine whether our lab-grown cells fit the bill,” Pekkanen-Mattila says.

As we continue our tour, doctoral student Kaisa Vuornos, member of BioMediTech’s Adult Stem Cell Group, pulls back curtains to show us a device that can shed light on the internal workings of cells. Under a fluorescence microscope, the nuclei of stained cells suspended in hydrogel are glowing bright blue.

“We stain cells using antibodies or fluorescent labels to determine the quantities of specific molecules within cells and to see what they look like,” Vuornos describes.

Any blood vessels in sight?

Markus Hannula, who is working towards his doctoral degree in the Faculty of Biomedical Sciences and Engineering at TUT, lets us inside a laboratory with formidable radiation warning labels on the door. The closet-sized X-ray microtomography device, micro-CT for short, standing in the middle of the room enables the 3D reconstruction of objects from X-ray images.

“The lead shielding makes the device weigh more than three tons. It was too large to fit through the door and had to be manoeuvred inside the lab through a new purpose-built window,” says Hannula.

The micro-CT works in the same way as brain scanners, which are often seen in medical TV dramas, but achieves a much greater level of detail. The device cannot be used on living specimens due to the hazards of X-ray radiation. Hannula shows us some of the images captured with the micro-CT, such as images of biomaterials and the auditory ossicles of rats.

“The advantage of using the micro-CT is that we don’t have to break objects to study them. Researchers use the micro-CT, among other things, to investigate cells grown in hydrogel suspension. For example, they can find out how cells are dispersed in the medium and whether they have formed structures, such as blood vessels. They can also extract detailed information on the CoE-developed biomaterials, such as determine their porosity,” Hannula says.

In the Sähkötalo building on the TUT campus, doctoral students Janne Koivisto, who specialises in biomedical engineering, and Olli Orell, whose area of expertise is materials science, are fine-tuning a device equipped with two cameras that are filming a piece of biomaterial being compressed between parallel plates. The process produces detailed information on the behaviour of materials under pressure.

“This type of data is utilised in the CoE, for example, while growing cells in a culture medium.”

Multidisciplinary approach opens up new research avenues

The CoE’s international atmosphere becomes evident as soon as one walks through the door. Researchers and doctoral students come from all over the world. We meet, for example, Scottish intern Kirsty Haddow and Nepalese researcher Chandra Prajapat, whose research interests are in cellular electrophysiology.

“One of our consortium’s strengths is definitely our extensive international networks,” says Mari Pekkanen-Mattila.

Another major plus is multidisciplinarity. For the CoE to achieve its ambitious goals, close collaboration is required across multiple scientific disciplines. The CoE brings together expertise, for example, in stem cells, biomaterials, micro- and nanotechnologies, sensor technologies, and biomodelling and -imaging.

“It’s wonderful to be working together with researchers from different fields. Sometimes we’ve been thinking out loud that we need a specific type of device to make headway in our research, and the researchers from TUT have immediately promised to build us one. Many of these ad-hoc research devices have since evolved a great deal,” says Mari Pekkanen-Mattila.

“Multidisciplinary research is extremely exciting. As an engineer, I enjoy seeing heart cells beat or nerve cells send signals and communicate with one another,” says Professor Pasi Kallio.


Text: Sanna Kähkönen
Video: Valtteri Kamppinen ja Valtteri Pönkkä
Photo: Valtteri Pönkkä