How do you build a human liver that could one day function normally inside a patient?
We've been working on the concept of building solid organs for quite some time now, and we have many different strategies. One strategy is to take a donor organ that's not being used and would have been discarded and, using very mild detergents, wash the cells away. Basically, two weeks later, you're left with something that looks a liver, you can hold it like a liver, it feels like a liver, but it has no cells. It's just a skeleton of the liver, the matrix, which we call the scaffold. Using that technology, we're able to reperfuse that scaffold with, ideally, the patient's own cells.
If using the patient's own cells is ideal, what happens when that's not possible?
Luckily, for the most part, we're able to use cells from the same organ, even if that organ is deceased. We use the progenitor cell population: the cells that have the potential to form the organ but have not been affected by the death of the organ. We like to use these cells because they're organ-specific cells and already know what to do. If you're going to make a windpipe, you want cells that already know that they're a windpipe.
What if the organ needing to be implanted in the patient just isn't available?
We very rarely have a case where you are missing cells from the organ in question, but if we don't have organ-specific cells, the next best choice would be stem cells from other parts of the patient's body. For example, if you're trying to make a liver, you may be able to get stem cells from the bone marrow to re-create the tissue of the liver. In this case, since you get the cells from the same body, there's no rejection.
The liver isn't the first organ you've built in the labyou've successfully implanted a lab-grown bladder. So what makes this development particularly noteworthy?
Building a solid organ like the liver in the lab is different and harder than with an organ like the bladder because solid organs are very vascular. When we process the liver, we actually have to preserve the blood vessel tree and perfuse it with blood vessel cells. Then we infiltrate the parenchyma of the scaffold with the liver cells. It's much more complicated. It's the difference between baking a cake and making a peanut butter and jelly sandwich.
Tell me a little about how these lab-grown organs are made. Is it a long process?
We start out by getting a cell tissue box from the patient, usually less than half the size of a postage stamp. Then we extract the cells from that piece of tissue to expand the cells outside the body in large quantities. Then we start composing the tissue very much like a layered cake, one layer at a time. Doing this, we're able to create the organ, and we put it into this oven-like device that has the same conditions as the human body37 degrees Celsius and 95 percent oxygen. We let the organ "cook" here, and usually two weeks after, that the organ is ready for implantation. So it takes about four weeks to grow the cells and about two weeks to create the organ. We usually give ourselves about eight weeks for the entire process.
How does the ability to grow organs (and tissues) change the current state of medicine?
There are more than 110,000 people currently on U.S. transplant waiting lists. And with current technologies, patients, for the most part, have to wait for someone else to die before they can get an organ and live, which is kind of ironic if you think about it. Every day, patients are waiting for organs, and they're getting worse and worse over time.
And, when a patient does get an organ from another person, it comes from a different body. It has different properties, and a person's natural tendency is to reject that organ. So the two major challenges today are tissue and organ rejection and shortage. That is where this field called regenerative medicine comes in, [bringing] together many different specialty areas to achieve a way to create ready-made organs and tissues for patients that are made from the patient's own cells.
You implanted the first lab-grown bladder into a patient already. How's she doing?
She's been doing very well. It's been four or five years since we published the paper, but she's had the bladder for over 10 years.
So what are the next steps for your work on the liver?
Right now we're making miniature livers. We're in the process of constructing larger segments that are at least four times as large as the current ones. Our ultimate goal is to make the livers larger and larger until we can get them to a size that can be implanted into a patient.
What are the main obstacles to achieving this goal?
The main obstacle is the vascular aspect of the organtranslating it to work in larger structures while preserving the same paradigm you see in the small livers.
Is it possible that we can build a heart?
Yeah, we're actually using the same strategy to build the heart as we are with the liver.
Can we expect to see miniature hearts soon then?
Absolutely, yes. We're building the heart currently using the human cells.
What about brains?
Absolutely. I think this same strategy could be applied to build most solid organ systems in the body.
Wow. So what kind of things would be transferred over? For example, when someone suffering from brain trauma underwent a brain implantation, would memories and skills learned over time remain intact?
The goal for us is to reproduce as many properties as possible. We test these organs at all levelsthe molecular biology, cell biology, physiology and pharmacology levelsbefore we implant them to make sure that they function the same way a human organ does.
So a lab-grown brain might function similarly to the brain of a newborn baby?
Do you ever see a day when we'll have mass-produced lab organs?
The future is certainly pointing in a direction. [But], since they come from the patient's cells, we'll still be making them individually.