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The tools that could help grow human tissue

Gold nanorods, modified with a silica shell, could help track the course of artificially programmed stem cells within the body. Image courtesy of Joan Comenge, University of Liverpool
Gold nanorods, modified with a silica shell, could help track the course of artificially programmed stem cells within the body. Image courtesy of Joan Comenge, University of Liverpool

Tiny gold rods and 3D scaffolds are just two of the tools helping scientists harness the power of stem cells to grow and repair damaged or malfunctioning tissue in patients.

Adult, or somatic, stem cells are distinct from embryonic stem cells and are found in many organs of the human body. They are useful because they are unspecialised and are able to replicate and give rise to specialised cells where there is damage, helping them act as a kind of internal repair system.

New types of engineered stem cells made from adult cells - known as pluripotent cells - have the potential to turn into different types of specialised cells through a process known as differentiation. In theory, if scientists were able to control this process they would be able to harness the cells to grow different kinds of human tissue inside and outside the body.

In one example of the possible applications, researchers on the EU-funded TissueGEN project are currently investigating how to induce pluripotent stem cells to become liver cells, in order to grow diseased human liver tissue to test new drugs.

‘Differentiating the cells into liver cells is challenging,’ says Dr David Hughes, chief technology officer at CN Bio Innovations Ltd, who is coordinating the project.

‘There's been a definite improvement in the field over the last few years, but it remains difficult to make stem cells become mature liver cells.’

3D scaffolds

To overcome this challenge, the researchers are trying to optimise three-dimensional scaffolds on which stem cells can grow, differentiate into liver cells, and ultimately reach full maturity as small units of human liver tissue a few microns across.

‘We have some interesting early results that suggest 3D is helpful for maturation of the cells and is something worth pursuing.’

Dr David Hughes, chief technology officer, CN Bio Innovations Ltd, UK

They are testing the theory that putting the cells into a 3D framework will drive their differentiation further towards maturity. ‘We have some interesting early results that suggest 3D is helpful for maturation of the cells and is something worth pursuing,’ said Dr Hughes.

There are many other factors that affect the differentiation process, all of which need to be optimised before their platform will be useful to the pharmaceutical industry.

CN Bio and its partner organisations are developing a number of different scaffolds to better mimic a human liver. They are currently using a scaffold made of polystyrene, and will next investigate softer, less rigid materials.

Seeding cells into 3D scaffolds can be difficult, with achieving a uniform distribution of cells throughout the scaffold a particular challenge. The scaffolds contain a series of channels that mimic the structure of a liver and its blood vessels.

‘In our system we use the fact that we have media flowing through the scaffold to encourage the cells into the channels,’ said Dr Hughes.

Internal repair

Cells that have been artificially reprogrammed to self-renew and differentiate into different types of cell, such as kidney cells, could also be used to regenerate or repair specialised tissue within the human body.

LiverChip scaffold Credit: CN Bio Innovations3D scaffolds can help researchers to grow stem cells, which can then be differentiated into many different types of cells, such as liver cells. Credit: CN Bio Innovations It’s part of the emerging field of regenerative medicine, an area of research in which adult-derived stem cells are used to repair or regenerate new tissue to restore normal bodily function. It also opens up the tantalising possibility of growing tissue patches from a patient's own cells to restore organ function when transplanted back into the body.

In order for such treatment to be effective, however, there needs to be a reliable method of tracking where the cells go when they are inserted into the body. Not only would this allow scientists to assess the efficacy of stem cell treatments, but it would also help them monitor the risk of adverse effects. Currently there are concerns that transplanted stem cells could go elsewhere in the body and cause tumours.

The EU-funded NANOSTEMCELLTRACKING project is developing a way of following the movement of stem cells in the body by labelling them with so-called nanoprobes, which emit a sound when they heat up.

Researchers are using nano-sized gold rods that can be put inside stem cells in their thousands and then employing a relatively new imaging technique called photoacoustic tomography to 'see' where the nanorods are located.

Living tissue is fairly transparent to near infrared radiation, but the nanorods aren't: they absorb the radiation, which heats them up by about a thousand degrees. The heat energy then passes into the cell near the nanorod and is converted into sound that an ultrasound device can detect.

These sounds can be reconstructed into a high-resolution image (around 150 micrometres) of where the nanorods are located, up to a tissue depth of five centimetres.

‘You start to lose resolution the deeper you go because of scattering,’ says Dr Joan Comenge at the University of Liverpool, who works on the project. ‘It's a really new technique, there are only two or three instruments in the UK.’

Currently, the penetration issue limits the technique's use for tracking stem cells in humans, but it is possible that photoacoustic devices will achieve deeper penetration in future.

For the time being the research is still at a fundamental stage. ‘We are in the safety part of this research,’ says Dr Comenge. ‘There are a lot more studies to do before it will be used in humans.’

Regenerative medicine remains a relatively new therapeutic field but scientists hope that tools like these will lead to a better understanding of the efficacy, safety and potential of using stem cells to treat disease.

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