Scientists edge closer to printing human tissue

A new technology early in clinical trials could make it possible for doctors to use specialized 3D printers to fabricate new human tissue based on a patient's own cells.

Known as commercial bioprinting, the technology from San Diego start-up Organovo starts with cells from adipose tissue--essentially body fat--or bone marrow and is intended to use those cells as the basis for making new tissue.

As of right now, the benefit for humans is still years away, perhaps as many as four, said Organovo CEO Keith Murphy. And when and if the company's technology gets certified and hits the market, it will probably have limited application: most likely, the technology could be used at first mainly for crafting very small areas of tissue or new blood vessels.

But even those limited applications could mean, for example, that doctors may eventually have the ability to intervene in cases where, for example, a patient has a blocked or damaged blood vessel, and potentially prevent what might otherwise result in a forced amputation. Similarly, someone with damaged nerves could have a gap in a nerve bridged using regenerated cells printed by Organovo's machine.

Doing something like making a new liver is still a long way off.

Still, to some observers, technology like Organovo's--while still a long way from helping an actual human patient--is encouraging.

"I think it's definitely important," said Daniel Kraft, a doctor and instructor at Stanford School of Medicine's Stem Cell Institute. "It's still very early days, but in the big picture, there's a lot of promise around stem cell and regenerative medicine."

One of the key functions of Organovo's technology could be to help overcome a traditional roadblock in regenerative medicine. "If you're ever going to be able to create organs outside the body, using stem cells or other techniques, it's important to allow that organ to connect to the blood supply of the patient," Kraft said. "One of the major challenges for tissue engineering is providing that blood supply, and what Organovo is focusing on is designing and printing the vasculature bed that is the foundation of any organs."

According to Murphy, the way to think about Organovo's technology is to think about the way a computer monitor or television is projected: in pixels. Organovo's technology, Murphy explained, is designed to work by making a 3D set of pixels of any set of tissue. "Then we replace whatever cell type is in each pixel and then put those cells in a matrix that we build."

The key to the process is a fusion of the full cellular aggregate. Murphy explained that Organovo's 3D printers--which are built by the Australian firm Invetech, using Organovo's specifications--lay out a bio-ink made entirely of aggregates of cells, which within a period of about 24 hours of being prone, fuse together.

According to an Organovo white paper, "Cells attach to other cells, and cells produce collagen and attach to collagen. Cells know exactly how to behave once placed in the right orientation by the printer. They behave the same way they do in the body based on their inherent genetic programming."

Ultimately, the idea is that the printer pushes out fused cellular aggregates and lines them up "like balls in a paintball gun," Murphy said, and then deposits them very gently, according to a design that a doctor can define with a "very simple script."

For now, the scientists at Organovo are focusing on blood vessels and other "tubular constructs" with very thin walls because of the reality that when trying to print any kind of tissue with any real thickness, the cells at the center will begin to die very quickly because of a lack of oxygen.

Rejection less likely
One big advantage of using Organovo's technology, Murphy said, is that because the tissue created using the company's 3D printers is based on a patient's own cells, "we don't have to worry about cells being rejected. The body recognizes them as having come from the same place...so that essentially removes that risk."

And that works, the company said, because cells that are originally taken from a patient are put into standard culture conditions and then grown. The bio-ink is then created using those cells, and built into a final tissue construct.

While Organovo's technology is still years from being certified for use, the company is already making its printers--which run hundreds of thousands of dollars apiece--available to "academic centers of excellence," Murphy said, "to allow them to do bioprinting with our technology."

And, Murphy said, the uses for the bioprinting technology are only just being discovered. "Wth the right funding, we think they can grow this by leaps and bounds...We hope researchers can see if [they can] get to larger and larger pieces of tissue by printing into their architecture...a branch of blood vessels."

If researchers are able to devise commercially-viable uses for the technology, Murphy added, Organovo hopes to become partners with them in taking the innovations to market.

Not inkjet printing
While Organovo's approach to bioprinting appears to be unique, there are currently others working on ways of printing new biological tissue, pointed out Stanford's Kraft.

He explained that Athony Atala, a researcher at Wake Forest University, has for some time been using reconfigured off-the-shelf inkjet printers for bioprinting (see video below). The idea there has been to print tissue that could be helpful to the thousands of soldiers who are injured in the wars in Iraq and Afghanistan.

But Organovo makes a point of differentiating its technology from what Atala and the Wake Forest team has achieved with inkjet printers by explaining that what it is doing is essentially rapid prototyping, and employs a process requiring no liquid and no nozzle.

"Organovo creates [the] bio-ink of discrete cellular aggregates, each made up of many cells," the company's white paper said. "These are used as a building block, as the bioprinter places these cell aggregates within high precision into a predetermined pattern."

To Kraft, the concept of using 3D printers to make new human tissue is an interesting one, but one he feels people need to have realistic expectations. Still, he also recognizes that technologies like 3D printing are showing phenomenal new promise and that the rate of change in the field is expanding rapidly.

"I don't think anyone should imagine we'll be printing complete organs in the next year or so," Kraft said. "But like 3D printing, bioprinting" seems like it has the potential for exponential growth. And that means it could just be a short matter of time before medicine and science conquer some of the limits in bioprinting that today seem insurmountable.