University of Texas Medical Branch at Galveston researchers have been awarded a two-year, $1.25 million National Institutes of Health grant to develop a method of custom-growing human lung tissue to make a three-dimensional model for biomedical studies.
The lab-grown piece of lung, about the size of a dime, will form the core of a system intended to provide a powerful new option for testing new vaccines and drugs and studying disease processes in the lung.
"I'm so excited that the NIH is giving us this opportunity," said UTMB professor Joan Nichols, principal investigator on the project. "We've been working on tissue engineering for a long time, and developing this kind of model has always been one of our goals. These systems could really change the paradigm of what we do."
The NIH is also funding 16 other projects aimed at developing similar models using engineered human tissues, including those for the heart, liver, kidney, intestine and skin. Ultimately, the agency hopes to connect different tissue models together, in order to create a system that could simulate the combined responses of multiple organs.
Although animal models for disease and pharmaceutical testing have a long record of success, experimental models based on engineered human tissues would offer significant advantages to researchers, Nichols said.
"First, it's a human system, and while you can simulate human responses with animal models, it's never perfect," she said. "Second, it's easily managed, and it scales up easily, because having no animal care makes everything cheaper and easier. And if the thing you're testing is toxic, it's just cells - you're not killing an animal."
According to Nichols, tissue-engineered models will also give researchers the ability to more easily conduct repeated observations in live tissue and apply advanced imaging techniques such as two-photon microscopy. They should also allow researchers to study diseases for which animal models are either nonexistent or prohibitively expensive, such as hepatitis C and Ebola.
To make engineered lung tissue for the project, Nichols needs to accomplish two main tasks. First, she has to generate a "scaffold," an extracellular protein network that will give structure to her creation. Then she has to add the right cells in the right quantities to grow tissue that will act as if though it's part of a real lung.
Nichols plans to either use an artificial scaffold or harvest a natural one from a pig lung, using a process that she and co-investigator Dr. Joaquin Cortiella developed to grow mouse lungs from stem cells. Choosing what kinds of cells to grow on the scaffold, she said, will be a matter of determining the best mix to accomplish two specific objectives: generating fibrosis, an all-too-common response to drug toxicity; and testing her system's responses to different strains of influenza.
"Like any organ, the lung has a lot of different cell types in it," Nichols said. "These tissues can be as complex as we want, but it's best to just start very simple and then build off of that - we can evaluate the responses of just pneumocytes, or endothelial cells and pneumocytes together, or endothelial cells and pneumocytes and immune cells, like macrophages and neutrophils. It's important to know what each individual piece does."
Nichols is confident that she'll be able to meet the goals the NIH has set for the two-year award, opening up the possibility that she'll be selected to participate in the three-year-long second phase of the project. "After this we will probably join with whoever got kidney, whoever got liver, whoever got skin and so on, as well as whoever's making the system that this will all go in," she said. "Then we'll have something really significant, with all these units linked together interacting with each other, very much like your body would normally."
UAB researchers reverse liver disease in mice with gene therapy