When people call Gordana Vunjak-Novakovic a tissue engineer, she corrects them. The professor of Biomedical Engineering at Columbia University says she’s not the one engineering tissue. “Only the cell is the tissue engineer,” she says. “We just provide the environment the cell needs to do the engineering.”
Vunjak-Novakovic and her research team have developed a way to use stem cells, biological scaffolds and bioreactors (culture systems designed to regulate tissue development) to enable regeneration that can fix hearts and bones. Their findings were published this spring. I talked with Vunjak-Novakovic recently; excerpts of our conversation are below.
I understand you’re growing new bones and hearts.
Sort of. It’s very exciting.
Tell me about the unique stem cell therapy that you’ve developed.
Our tissues can only be generated by living cells. You can do it outside the body, so you can make a piece of bone to reconstruct if someone has a shattered face, for example, and then implant that, or you can implant a patch of the heart. In both cases the tissue will continue to develop in the body because they are always implanted half-baked. Through the development, it is integrated with the adjacent tissues, as it should, and it is remodeling—adapting to the specific local conditions in the body. So this is one approach. The key is some kind of a stem cell. They can be instructed to go one way or another.
The important thing is that the cell is the only and ultimate tissue engineer. People will say, "She is a tissue engineer,” and I’ll say, “I’m not; only the cell is the tissue engineer.” We just provide the environment the cells need do the engineering. This is why we often say we are just mimicking what happens in nature.
If you break your bone, it’ll heal; but it’s important to understand what happens in successful, normal healing. Adults regenerate slowly; young people regenerate quickly. Fetal is very, very fast. So it's part of tricking the cells—providing them with factors that they normally see during early development. This is where stem cells come into the picture. If you take old cells, adult cells, they’ll do the job but it’ll take approximately forever.
You said the tissues are always implanted “half-baked.” How do you know how much to “bake” them?
We really don’t know. If you could place just stem cells in some kind of carrier into the body, they have this ability to turn into many different types of cells. You need to tell them to become bone or become heart or blood vessel, so you have to push them down that path. The whole objective of implantation is providing function that they’re missing in the body. If you do that too early, it won’t function. It may result in total lack of function or cells that are disoriented/don’t know what to do. All our experiments show us if you push the cells down a specific path they do a much better job after implantation.
On the other hand, if you place totally developed tissue—such as bone from one part of the body into another part—bonding is very slow because there is no development. We know [the ideal time is] somewhere in between, but how much is enough, we honestly don’t know. You definitely want to pass the threshold; you also want a little bit of functionality: cardiac muscle needs to twitch, bones need strength. But how much you really need depends on many known and unknown factors; I also think there’s no single optimum for everyone. We’re entering the era of personalized medicine—someone is old, someone is young, someone has diabetes, these all affect it.
Which patients will benefit from engineered hearts and bones?
There are two things that are really important—today we’re living longer and better than we used to. One orthopedic surgeon I talked to is operating on people between ages 14 and 88. There is an expectation to have a higher quality of life for a longer time.
Also, none of the prosthetic devices are doing a good job. They need to be serviced, they need to be replaced. If you have titanium in your head, it doesn't grow or shrink with the person’s body. This can renew our tissues so we can be serviced in a much better way. I think patients can greatly benefit from getting something very similar to the tissue they lost.
Eighty-five percent of all lungs that are received for transplantation—and it’s very difficult to get one quick enough—they need to reject for various reasons. So there is an enormous need to make in a laboratory tissues or organs. Although we are not there yet with organs.
The benefit is to have your tissues repaired or replaced with something biological—to use the patient’s own cells so they get their own piece of cartilage, their own piece of bone. It’s ideal if you can do that.
How do you determine the shape of the bones?
To make something in a precise shape is very easy. If you need to replace something, you need to take images of the piece you’re missing. Then you construct them into a three-dimensional file. This is technology that has been established before. You use the same data to make a chamber, which will be like a negative. Your scaffolding material is placed into a very soft plastic material and then you load it with the cells and culture it for a period of time
So it really is like baking.
Yes, very much. But instead of like a cookie cutter it’s something a little more fancy.
How are you testing it?
At three different levels. We can test in vitro. Then animal studies in mice and rats, which we have done. You implant a little patch or a piece of bone into the small animal and see how it integrates and functions. Then you move to large animal studies, such as facial reconstruction in a pig. I’m told that anything that works in pigs they would be ready to move to human patients. We will probably start in large animals in June.
Who is funding this?
[At this point] you are sort of too far along to be funded by NIH, which funds science, but it is too early to be funded by biotech investors. It’s what some people call the valley of death—the in-between area. So everyone is looking for bridge funding. We got $250,000 from the BioAccelerate NYC Prize. We want to get to the point where we can talk to the commercial sector and show that we have something that’s been validated.
Photos: Gordana Vunjak-Novakovic