Immunologically Customized Hearts to Order

Researchers in the Texas Heart Institute in Houston have found a novel way to craft 3-D organs like hearts, kidneys, and livers – all of which are extremely high demand for transplant.  Right now the technology is limited to fairly simple, hollow structures like trachea and bladders, but a method had been developed to use the collagen support structure the transplant organ itself as a scaffold … which is then repopulated with immunologically matched stem cells to prevent rejection by the new host.  The kicker is that it doesn’t even have to be human in order to work.  Got a pig heart?  Great!  Rinse it out with some detergent to dissolve the cells, replace them with something a little more human, and we’re good to go!

CLICK TO EMBIGGEN (pic from Nik Spencer, Nature)

Sounds simple enough, right?  I’m glad I’m just an engineer … I’m leaving this for someone who knows what they’re doing.  For example, I wasn’t joking about using pig hearts, or detergent to strip away its cells – that’s literally what they do:

The tricky part, Ott says, is to make sure that the detergent dissolves just the right amount of material. Strip away too little, and the matrix might retain some of the cell-surface molecules that can lead to rejection by the recipient’s immune system. Strip away too much, and it could lose vital proteins and growth factors that tell newly introduced cells where to adhere and how to behave. “If you can use a milder agent and a shorter time frame, you get more of a remodelling response,” says Thomas Gilbert, who studies decellularization at ACell, a company in Columbia, Maryland, that produces extracellular-matrix products for regenerative medicine.

Thankfully, they’ve done this on so many hearts that they’ve refined the process fairly well.  Though, as the article points out, this is probably the part that has reached the greatest level of maturity.  Re-cellurization, or the process of re-growing the heart with human cells – has more unanswered questions.

‘Recellularization’ introduces another slew of challenges, says Jason Wertheim, a surgeon at Northwestern University’s Feinberg School of Medicine in Chicago, Illinois. “One, what cells do we use? Two, how many cells do we use? And three, should they be mature cells, embryonic stem cells, iPS [induced pluripotent stem] cells? What is the optimum cell source?”

After that, getting them to grow on the scaffold in a biological environment that closely mimics the heart is the next hurdle.  Taylor and her associate Harald Ott have been able to successfully mimic enough of the conditions of the heart using an artificial bioreactor to create “new” hearts from rats and some larger mammals to pump up to 25% of their original capacity.

The largest problem, at this point, is their longevity after transplant.  Again, the hearts don’t do much good at partial capacity.  Some lungs and kidneys were transplanted, but they malfunctioned shortly after the operation, likely due to an incorrect proportion of certain cell types needed for specific tasks.

In other words, full-organ replacement is not even close to easy, nor is it ready for prime time for what I would guess to be a decade or two.  The good news – according to researcher Stephen Badylak of the University of Pittsburgh – is that within about 5-7 years, we may have enough expertise to enable live replacement of faulty heart valves or the lobes of a lung, or a liver.  I can still hold out hope that by the time my organs start failing, modern medicine will be at the point where they’ll be able to just print me a new one.

I plan on living forever, after all.

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