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Sunday, November 1, 2015

Creating a human kidney in the lab to treat kidney failure: Reality or Star Trek?

I look at the artificial kidney that I talked about in my last post as a sort-of futuristic automaton. It can work (in principle) on the body's internal power (the blood pressure) and does not require the frequent tweaks (again, in principle) that are required with conventional dialysis; thus giving patients more freedom with their lives.


However, the technology that really has the trans-humanist in me jumping up and down with excitement is the promise of regenerating a "natural" human kidney in the lab. In Greek mythology, Prometheus' liver would regenerate even after an eagle nibbled on it every day, all while the poor fellow lay chained to a rock (he was lucky the eagle didn't mess with his kidneys, which don't quite possess the same regenerative capacity!). My fantasy is not quite the same, but what I had always conceptualized is that with the advances in regenerative medicine, we might be able to just play God, and "make a kidney", a real human kidney, not a chimera of materials from man and machine. It always seemed to be the stuff of science fiction.



Prometheus, as depicted in "Prometheus Bound" by Sir Peter Paul Rubens
The original painting is at Philly's Museum of Art



This fiction might become a fact within our lifetimes. One place which is really doing cutting edge work in this field is Wake Forest University's Institute for Regenerative Medicine. Initially, researchers working on animal embryos had demonstrated  that if you take early precursors of kidney tissue and transplant them in to animals, the precursor cells can grow in to a cohesive structure that can make urine, and even produce the hormones that an adult kidney normally would (vitamin D, erythropoietin). As you might imagine, this is a useful "proof on concept"; however, it has ethical implications before it can be used in humans. Any kind of research and clinical application using human embryos as a source to "harvest" kidney tissue/cells would face tremendous regulation; that is, if it ever got approved.


Which is where our final, and perhaps most promising technology comes in. This involves using stem cells and arranging them along a "scaffold" to help them grow in to a real kidney. Stem cells are the precursor cells of every single cell in your body. They have the ability to "mature" in to any type of specialized cell depending on which genes are switched on/off in those cells. Think of your kidney cells, and your liver cells, and your skin cells as being "cousins". And their common parent is that stem cell. Using specific signals, scientists can coax a stem cell in to maturing in to a kidney cell vs. a liver cell!


So you now have one of the ingredients required to make a kidney: the stem cells. However, the human kidney has multiple types of cells. You have the epithelial cells along the kidney's filtration apparatus. You have the cells of the blood vessels. You have specialized cells that hold the architecture of the kidney together, known as the fibroblasts/fibrocytes. So the next challenge is: how do we mold these different cell populations together so that you end up with a structure that at least resembles a normal kidney? Scientists are attempting to solve this problem by using a scaffold. This would be a "skeleton" that comes pre-made with some of the cells mentioned above, and then you flesh out this skeleton using stem cells!


One ingenious way of creating this skeleton is to take a dead kidney (animal or human), and decellularize it using detergents. You are then left with a scaffold which provides a niche for stem cells, and guides them along as they grow in to a kidney. But, my vote for hands-down-the-coolest technology that exists for creating this scaffold is "bioprinting". With this, you actually use a modified ink-jet 3D printer to lay the essential cells in any design you want, and essentially "print" yourself a kidney! Here is a video illustrating this process (fast-forward to 10:30):





I want to believe that when it comes to treating my patients with kidney failure, "the future is here". However, in all probability, these technologies could still take years, potentially a decade or two, before we could safely dump dialysis. But I do foresee it happening within our generation. Certainly, the implantable kidney that I talked about in my last post is expected to see the light of the day sooner, with clinical trials supposed to start in 2017.


    

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