A 3-D Printer for Human Embryonic Stem Cells

Researchers hope to one day be able to print out an entire human liver

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Steven Cherry: Hi, this is Steven Cherry for IEEE Spectrum’s “Techwise Conversations.”

3-D printing is being used for all sorts of things, from small plastic parts and microprocessors to a titanium jawbone for transplantation, from wedding cakes, as we’ll be describing in an article in our June issue, to an entire car body, as we’ll be hearing about in a podcast next month. Everything from computer chips to chocolate chips, in other words.

But the most unusual and potentially one of the most beneficial uses has to be that of human embryonic stem cells.

This is a pretty new thing. Researchers have done this with the stem cells of other animals, but it was only last month that a team at Heriot-Watt University, in Scotland, announced the 3-D printing of human stem cells. The work was published in the journal Biofabrication. My guest today is one of the coauthors of the study.

Will [Wenmiao] Shu is at the School of Engineering & Physical Sciences; Biochemistry, Biophysics & Bioengineering at Heriot-Watt University. He joins me by phone from there.

Will, welcome to the podcast.

Will Shu: Hello. Hi, thank you for inviting me.

Steven Cherry: The title of your paper is “Development of a Valve-Based Cell Printer for the Formation of Human Embryonic Stem Cell Spheroid Aggregates.” That’s certainly a mouthful, so let’s take it in parts. What you did here was actually build a printer.

Will Shu: Okay, so there are two key components of the 3-D bioprinter. One is the printing nozzle, which determines what kind of materials you can print and also how much quantity of the material you can print at a particular spot, okay. So the valve-based printing nozzle we developed is basically, are solenoid microvalves, which we found is very gentle in printing stem cells, human embryonic stem cells.

So the printed human embryonic stem cells intend very high cell viability. And also, importantly, after printing out, we found the stem cells kept their key biological function, which is their potency—their ability to be turned into any other type of cells in the body. And the other key component of the printer is basically their motion control. And similar to other types of 3-D printers, which you can print plastics [unintelligible] three-dimensional motion of the printing head, basically how well you can print, and that’s quite similar to other types of 3-D printing technology.

Steven Cherry: Now, this business of human embryonic stem cell spheroid aggregates: What are those?

Will Shu: Basically, cell aggregates are actually tiny balls—okay, you can call them tiny spheres, or tiny balls—made up of hundreds of stem cells. Stem cells tend to aggregate together. They would not survive in single cells, especially human embryonic stem cells—they like to aggregate together and form these three-dimensional objects, or microtissue we call “spheroid cell aggregates.” They are very tiny, usually smaller than 1 millimeter.

Steven Cherry: There’s a medium in which this printing is done. Two of them, actually. Why are they needed, and why two of them?

Will Shu: Well, basically we use the medium to generate the gradient of sizes of cell aggregates. There are stem cell culture media. But one with human embryonic stem cells, the other without human embryonic stem cells. So in the process, we combinatorially print them together, okay? Then we can generate a droplet with different cell numbers in each droplet. Therefore, in each droplet we can form cell aggregates with different sizes.

Steven Cherry: By the way, is it fair to call this business of printing cells “copying cells”? I mean, do you basically start with a cell and copy it?

Will Shu: Sorry, you mean, copying?

Steven Cherry: Yeah, you start out with a…

Will Shu: Single cells.

Steven Cherry: Yes.

Will Shu: Yes. Yeah. So we print—we start with single cells and then arrange them so they can aggregate themselves to form these three-dimensional objects. Using the same technology, we can also print cell aggregates directly so that we can form a larger tissue.

Steven Cherry: Now, you were creating liver cells. Why did you choose them?

Will Shu: Well, we are interested in generating liver cells, or liver tissue, because they are very important for screening drugs. Drugs will be metabolized in the liver, so this is very important tissue to test the toxicity of drugs. A lot of this drug testing now by pharmaceutical companies are based on either animal cells or using animals directly. So the ability to print and generate 3-D human tissue will allow us to generate a human tissue model for this drug testing. Therefore, hopefully, we can eliminate the use of animals for drug testing.

Steven Cherry: Which is good for animals and humans as well, and I guess on principle you could start with an individual’s cells and print an individualized liver or kidney, and rejection issues would be diminished.

Will Shu: Exactly. That would be the future of personalized medicine. Although it will be more expensive to do that. I’m sure one day we can make the technology cost enough for everybody to test their drug before taking it.

Steven Cherry: It’s more expensive at the front end, so to speak, but when you reduce rejection issues, you save money in the long run.

Will Shu: Indeed. Well, we have short-term and long-term goals, okay? The first is short term: We would like to use the technology to generate 3-D stem cell tissue and turn that tissue into liver tissue. Human liver tissue. So that’s our short-term goal. And in the longer term, we expect to use the technology to generate our whole liver organ. To do that, we need to introduce these delicate vascular structures inside the organ to transport nutrition and also remove the waste so that the organ can survive in [the] long term.

Steven Cherry: Do you think that would be one day possible? I guess with multiple print heads you could be creating—layering on different cells, such as the vascular structure.

Will Shu: Yes, I think we [unintelligible] biofabrication field in general, we should be able to not only print different cell types but also generate these three-dimensional structures, very delicate three-dimensional structures, in order to replicate a process of generating an organ using 3-D printing technology.

Steven Cherry: And would such an organ be one that could be used for transplantation?

Will Shu: Yes, that would be the long-term goal. To be able to in vitro generation of an organ ready for medical transplantation.

Steven Cherry: Now, in the early days of stem cell research, there were some limitations erected around the use of human embryonic stem cells. Do any of those issues remain?

Will Shu: There are certainly still ethical issues, because in order to generate human embryonic stem cells, you need to destroy early-stage embryos. So that ethical issue is still there. However, once you have the human embryonic stem cells, they can be replicated in the lab indefinitely. So that means you can have and use this cell line for making human tissue or organs in the future.

There’s another way to get around that, which is another stem cell technology called iPS cells. You probably have heard of it already. They can be generated without destroying human embryos. You take them from cells, like skin cells, and then back to the embryonic stage, which are indistinguishable to human embryonic stem cells. But that technology is still not as mature as human embryonic stem cells. So currently we are using human embryonic stem cells to demonstrate the possibility to generate human tissue and a human organ. In the longer term, we expect iPS technology would catch up, and therefore we would not have to face the ethical issues that come with human embryonic stem cells.

Steven Cherry: What are some other uses for this printer?

Will Shu: Well, there are a variety of other potential uses. The technology shows that the printing process is very gentle to cells like human embryonic stem cells, so if we can print highly viable human embryonic stem cells, that means we can also print other types of cells directly. So, for example, we can print liver cells directly. We can print any cells directly. So I would suspect this technology can be used for printing other types of cells in forming adult tissue directly.

Steven Cherry: And that would eventually lead to creating entirely new organs—new kidneys for transplantation, new lungs, and so forth.

Will Shu: Yeah, that can certainly be used for that application. Actually, another application we put in the conclusion part of our paper is it would be possible to use the printing nozzle to directly print a cell inside our body in order to repair a tissue. For example, if you have, or a patient has, a damaged tissue in the heart, it would be possible to directly print a heart tissue inside the body using [a] less-invasive method, like laparoscopic surgery, to directly insert the printing head so as to directly repair the organ inside you.

Steven Cherry: That’s quite remarkable. Well, it’s generally a remarkable sort of research. People have all sorts of organ disorders and diseases these days, and transplantation is becoming a rather straightforward matter. The main problem is the lack of healthy organs themselves. So good luck to you as you continue your research, and thanks for joining us today.

Will Shu: Thank you very much.

Steven Cherry: We’ve been speaking with Will Shu of Heriot-Watt University about a 3-D printer that prints human embryonic stem cells and might someday print an entire liver.

For IEEE Spectrum’s “Techwise Conversations,” I’m Steven Cherry.

This interview was recorded 6 March 2013.
Segment producer: Barbara Finkelstein; audio engineer: Francesco Ferorelli

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