Decellularisation! Organ scaffolds!

Hybrid hearts could solve transplant shortage

"It's amazing, absolutely beautiful," says Doris Taylor, describing the latest addition to an array of tiny thumping hearts that sit in her lab, hooked up to an artificial blood supply.

The rat hearts beat just as if there were inside a live animal, but even more remarkable is how each one has been made: by coating the stripped-down "scaffolding" of one rat's heart with tissue grown from another rat's stem cells.

The idea is fairly simple: take an organ from a human donor or animal, and use a mild detergent to strip away flesh, cells and DNA so that all is left is the inner "scaffold" of collagen, an "immunologically inert" protein. Add stem cells from the relevant patient to this naked shell of an organ and they will differentiate into all the cells the organ needs to function without inducing an immune response after transplant, or any new infections.

Although Taylor only added stem cells to the hearts, these cells differentiated into many different cells, in all the correct places, which is the best part of using decellularised scaffolds. The stem cells transformed into endothelial cells in the ventricles and atria, for example, and into vascular and smooth-muscle cells in the spaces for blood vessels, just as in a natural heart. Taylor thinks this happened because she pumped blood and nutrients through the organ, producing pressure in each zone which helps to determine how cells differentiate there.

But chemical, as well as mechanical, cues seem to have guided differentiation. Taylor has evidence that growth factors and peptides remained anchored to the scaffold even after the flesh was washed off. These chemicals likely signalled to the stem cells, indicating how many should migrate to which areas and what to change into in each zone. "Our mantra is to give nature the tools and get out of the way," she says.

Also: Stem cells used to restore sight

The idea to team stem cells with contact lenses came from an observation that stem cells from the cornea stick to contact lenses. To obtain the stem cells, Dr Watson took less than a millimeter of tissue from the side of each patients' cornea. Working with colleagues at POWH and UNSW, he cultured stem cells from the tissue in extended wear contact lenses.

Within 10 to 14 days the stem cells began to attach to the cornea, replenishing damaged cells. Satisfied that the stem cells were doing their job, Dr Watson removed the lenses and the patients have been seeing with new eyes for the last 18 months.

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11 Responses:

  1. autodidactic says:

    That kid who had his eyes eaten by that Dad on PCP... I hope that science can help him out, and maybe that bottom article is the way.

  2. gwynjudd says:

    So you could use this to create a whole person, right?

    • curgoth says:

      "The idea is fairly simple: take an organ from a human donor or animal, and use a mild detergent to strip away flesh, cells and DNA so that all is left is the inner "scaffold" of collagen, an "immunologically inert" protein."

      Sure, but you'd have to take apart another person first.

      • maramala says:

        Well, you could always take parts from corpses, it's not like they're going to be needing them any more--

        Okay, we're thinking too hard on this.

        • gryazi says:

          This probably is a point, though. The ideal would be to injection-mold the scaffolds, spray on any helpful markers discovered through research like this, and let everyone grow a couple spares and keep 'em in the fridge (or on the coffee-table, quite a conversation piece)... But in the meantime, live organs are damn fragile and need to actually stay in functioning shape to drop-in; the collagen probably stays 'fresh' much longer, so a donor organ that's not quite ripe for transplant for one reason or another could still wind up saving a life.

          Perhaps this'll also work out for 'close-enough' transplants from food animals... not really a pleasant thought, but we're certainly freeing up lots of potential scaffolds from them every day.

          • IF we did this in people it would avoid rejection. Normally, the transplanted heart has lots of markers which identify it as foreign. Their immune system would immediately set about trying to isolate it from the rest of the body and kill it. To prevent this transplant patients take immune suppressing drugs for the rest of their lives. This leaves them vulnerable to infectious diseases. So they also take more drugs to try to kill off anything nasty before it kills them. This is expensive and still messes up their lives. Sure, they're alive, but they're reminded every time they take those pills that they're on a short leash. It's not uncommon for patients to bend and even break the rules, a glass of champagne at a grand-daughter's wedding becomes a G&T every afternoon, and then they pretend they have no idea why they're having problems...

            But a heart made from your own cells does away with this. The immune system recognises it as self, and instead of actively trying to destroy it, will help protect it. You could be home quicker, with just some dietary advice and a few routine follow-up appointments to make sure the surgeons didn't screw up. Using a scaffold could become the gold standard in transplants targeting "priority 2" patients - those healthy enough to wait some time for a new heart.

            But first we have to see if the "growing a heart" trick works on humans. Then we have to see if the resulting hearts work when transplanted. Then we have to see if the people who get them live normal lives or suddenly drop dead a few weeks later. Maybe they'll have the kinks worked out in 20 years.

  3. maramala says:

    Oooh, bioware! My inner mad scientist approves of this.

  4. rhino_rex says:

    all of this is just going to keep Baby Boomers around that much longer.

  5. pavel_lishin says:

    I guess we're going to skip right past the organ bank problem.