Ghost hearts, meat berries and transdermal implants
Content warning: This article contains images of internal organs and may be Not Safe For Work.
What would happen if you were to remove all of the cells from an piece of fruit? What about an organ or other tissue? Contrary to what you might expect, there would be a lot of stuff left over. For plants, most of that ‘stuff’ would consist of cellulose and lignin (the main components of paper and wood). Animals are a bit more complicated and a lot less ‘woody,’ so the leftovers would mostly be collagen, and other connective proteins like fibronectin and connectin.
The process of decellularization actually allows you to see these outcomes for yourself. During this process, all the cells are washed away, leaving only connective tissue and little cell sized pockets behind. After the process, you can take new cells and grow them into the existing scaffolding of little pockets, and in a sense, breathe new life into the tissue. The best part is, some of the biological markers that tell cells “this kind of cell is supposed to grow here” are also left behind, so the new cells will even differentiate and form complex tissues. The first time this regrowth experiment was done, researchers decellularized a rat heart to produce a ghostly white scaffold. They then reseeded it with new rat heart cells, and eventually they managed to get the newly grown heart beating again.
For patients needing new organs, this could be revolutionary. With no worries of donor organ rejection, a doctor could just grow them a new heart made of their own cells. There would be nothing to reject, because in a sense, the new heart is still theirs. Recently, a professor at the University of Ottawa showed that the process could not only work on plant tissue, but that you can grow animal cells on the scaffolds generated from plant tissues. He’s currently using the technique to grow human tissue on apple slices shaped like ears.
Suffice it to say, when I first heard about this process, I was enthralled and had to try it. Luckily, decellularization has been studied in depth on almost every kind of organ and tissue, so finding instructions was relatively easy. The University of Ottawa professor, Andrew Pelling, wrote an in-depth paper on his process so I started with that.
Fruit and vegetables are surprisingly easy to decellularize. First, you freeze the piece of tissue (I trialed apples, kiwis, strawberries, broccoli and a mushroom) to poke holes in all of the cells. Then you submerge the tissue into a 2% solution of sodium dodecyl sulfate (SDS), which is the main component of most soaps. It’s a surfactant that is really good at washing away oils and lipids, and since cell membranes are made of lipids, they get washed away along with everything inside the cells. The process is beautiful to watch and the kiwi put on the best show. As the cells were being washed away, a silvery fluid could be seen dripping out of the fruit tissue. In a sense you could literally watch the life drain out of it. Eventually, when all was said and done, I was left with beautiful white scaffolds in the shape of the various fruits and vegetables, totally devoid of cells. For those interested in trying this process, I made a video going through the steps in detail.
Once the fruit and vegetables were finished, I decided it was time to try something a bit more difficult. I went to the local butcher shop and convinced them to sell me an intact pig heart (normally they’re only sold butterflied). They gave me some weird looks, so I told them it was for a school project (a liberal bending of the truth). With heart in hand, I got ready to do the decellularization. Unlike fruit, the process for animal tissue is a bit more complicated, and I ended up following a procedure on Instructables that goes into immense detail on the process. In short, you attach a hose to the aorta and force liquid through the heart in the opposite direction that it normally goes. This is called retrograde coronary perfusion. Rather than just SDS like with plant tissues, animal tissues require several washes of different solutions. This is because animal cells are much smaller and harder to wash out. Just like the fruit, I made a video going through the whole process.
Over the course of a few days I watched the heart go from blood red, to ghostly white. I should note that the purpose of this first attempt to make a decorative piece, so the compounds I used are not ideal. In a professional setting where the scaffolds are meant to be used for cell culture work, different solutions are used as they are much more gentle and do less damage to the various connective proteins. For my experiment, I used what I had at hand.
At this point the mad scientist in me was already cooking up all sort of ideas. Firstly, what would happen if you were to grow cow muscle on one of the decellularized strawberries? Could you make a meat berry? And what if you did it in reverse, could you decellularize a steak and grow plant cells on the scaffold? But beyond building deceptive meat berries and plant steaks, decellularization provides a very powerful tool for growing cells into very complex shapes so there’s an incredible amount of room for experimentation. The aspect that I find the most interesting are the biological markers that are left on the scaffold. If one were to decellularize a piece of tissue and freeze dry it, the resulting powder could be used in much of the same way as the original scaffolds. On contact, it tells the growing cells what sort of cell they should become. So if you start with bone tissue, you can make bone cells grow, or if you start with heart tissue you can make heart cells grow. The immediate implications of this are in things like 3D bioprinting. It could allow for easy 3D printing of biological scaffolds in incredibly complex shapes, all with the biological instructional signals for the cells built in.
One of my other project is already poised to benefit from this technique. Transdermal implants are those that sit partially below the skin, and partially above exposed to air. No matter how well they heal, there is always microscopic gap between skin and implant that allows bacteria to get in. This can mean they get infected, reject, and thus have to be removed. Currently our best methods only work a fraction of the time. For aesthetic implants this isn’t such a big problem, but for medical implants this can have very serious consequences. For a long time we’ve needed a new coating that would allow skin and implant to fuse without that gap. My friend Gabriel Licina and I have been exploring making such a coating for a while now and decellularized tissue has always been on our list of possibilities as an ideal material for such a coating. So hopefully soon, transdermals will get consistently safer, organs will be more readily available, and maybe we’ll even have meat berries, all thanks to a simple but powerful technique that can be done at home.
