Micro Organs in Miniature

With new understanding about the structures of human organs, scientists are growing miniature human livers, hearts and kidneys and linking them together with a blood substitute, to evaluate the effects of new drugs.

WINSTON-SALEM - Whether it’s the Ebola virus, a new treatment for diabetes, or even a chemical weapon such as sarin gas, the key to developing a treatment is having an effective medicine.

However, developing that medicine can take years and cost tens of millions of dollars. That’s because those medicines cannot be tested on just one organ alone. There are about 60 different organs or pairs of organs in the body, such as the heart, kidneys, and even the skin. Researchers and regulators must know the short and long-term effect of a medication on specific organs as well as the body before any medicine can be approved. Their short and long-term effects on the entire body must be analyzed.

Researchers at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine hope to make it easier to evaluate medicines by creating a body on a chip.

That’s right, a chip.

Let’s start with Ivy Meade. She’s a research assistant at the Institute and uses a special microscope to study 300-micron wide sections of cells. She’s showing me a section of liver that resembles a small seed pod you might find in the forest.

“This is a spheroid that’s been colored red to help us identify what chemicals it is producing,” says Meade, pointing out different features on the liver cells. "This shows they are healthy, and I like this one because not only can I see it is producing a cohesive ball of cells, but I can see the texture of the cells, and the channels, and that allows for oxygen and nutrients to get into the cell, otherwise the cells in the middle start dying.”

What’s amazing is that the living cells we are studying didn’t come from a human body but from a plexiglass chip. The chips are small rectangles of clear plexiglass, roughly three inches long by one inch wide. We found them in another lab at the institute. Sandwiched between two chips is a small chamber with a pink gel inside. Imagine strawberry jam sandwiched between the two rectangles and you get the idea.

“To get a working micro liver, heart or lung, you first need the cells,” explains Dr. Aleksander Skardal, a researcher working on the project. “You can get them from a variety of sources such as human tissue, stem cells, there are many ways to do it, but the key is to have living cells.”

The cells are then combined with a polymer matrix or proteins to create a gel, which can support the cells.  This living gel mixture is then placed into a bio-printer. It’s similar to an ink-jet printer except it uses biological material. The gel is deposited into a three-dimensional form. The collection of approximately 200,000 liver cells eventually begin working together and take on the function of a working liver.

Repeat the process with the cells from other organs and then, once a set of micro-organs is created, they can be linked together with a synthetic blood substitute. Eventually, a collection of miniaturized human organ-like hearts, lungs, and livers can be collected on a countertop.

Dr. Skardal showed me what this countertop collection looked like. The clear glass chips were set out side by side, with thin coils of clear tubing linking them together. The red blood substitute was flowing through the tubes. A small pump off to the side was moving it along.

“If it it looks a bit like an electrical circuit you are right on target,” explained Dr. Skardal. “That’s the concept behind the program,” a program titled, appropriately enough, “The Body on a Chip.”

“It’s a very simplified system, but it allows us to look at the complex interactions of the body without having to do it in a human or an animal,” says Dr. Skardal.

The military is funding this unique $24 million project. The Space and Naval Warfare Systems Center Pacific, on behalf of the Defense Threat Reduction Agency, awarded the contract. The other partners in the project include Brigham and Women’s Hospital in Boston, the University of Michigan, the US Army Edgewood Chemical Biological Center, Morgan State University and the Johns Hopkins Bloomberg School of Public Health.

The goal is to build a miniaturized system of human organs to model the body’s response to harmful agents such as chemical weapons. But it can also be used to test the effectiveness of new medicines. The system could save millions of dollars and reduce by several years the development cost and time for new drug therapies.

“We are modeling the response of a tissue to certain chemicals,” says Dr. Shay Soker, a professor of regenerative medicine. “And we want this model to be as reliable and as perfect a replication of what is going on in our bodies as we can make it.”

Dr. Soker explains that once all of the cells are on the chips, in the correct composition and orientation to represent whatever organ is needed, the cells begin to function as they would in the body. That means once scientists introduce a drug into the synthetic blood stream and that drug diffuses into the tissue, the cells will respond in exactly the same way they would in a human being.

“What happens then is that some of the cells will take the drug and change it a little bit,” says Dr. Soker. “So a drug that may not have been toxic before, once it goes to the liver, may become toxic. And then, if that drug happens to have some cardio-toxicity to the heart, once it gets into the circulation, and then to the heart, we’ve got problems.”

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