Regeneration of a solid organ for transplant can take years to reach patients. But regenerative medicine technology as an instrument for discovering and testing new drugs? It’s already happening.
In Winston-Salem, North Carolina, scientists are 3D printing miniature organs that model the anatomy and function of the heart, liver, lungs and even the brain, said Anthony Atala, a professor of urology at Wake Forest University. Their “lifetimes” are only months, but that’s more than enough time to evaluate a drug in ways that laboratory tests or even animal studies cannot.
“After investing tens of millions of dollars, 90% of these drugs will fail if a drug is accepted into a phase 1 clinical trial through the FDA,” said Atala on March 24 at the Oracle Health Sciences Connect 2021 conference. “It’s because of the tests, which aren’t really accurate. Hence the strategy is to create these miniature organs. “
Atala is the director of the Wake Forest Institute for Regenerative Medicine (WFIRM), which studies about 40 different tissues and organs. So far, the institute has launched 15 technologies that use human cells to construct tissues and organs.
The drug tests take place on organoids, an in vitro system that stands for an organ. These miniature organs can be made in both healthy and diseased states, Atala said. These chips can produce the human equivalent of physiological responses. For example, scientists can induce a heart attack or a stroke to assess what a drug would do to an organ affected by these conditions.
WFIRM’s drug research represents a convergence of technologies. This body-on-a-chip technology is used to screen libraries of compounds for safety and efficacy prior to animal studies and clinical trials, Atala said. The data is cataloged at every step of the process. Artificial intelligence can then be applied to find patterns in the data, thereby improving predictive modeling for drug development.
Wake Forest research is conducted as part of the Humanoid Sensor Consortium, a partnership made up of pharmaceutical companies, academic institutions, and government agencies. WFIRM’s own drug discovery workforce includes the Biomedical Advanced Research and Development Authority (BARDA), which has allocated $ 25 million to research potential countermeasures against chemical agents. The Defense Threat Reduction Agency (DTRA) has allocated more than $ 26 million to develop countermeasures for nerve agents.
The technologies that are closest to patients are part of a new approach to personalized medicine. The miniature organs help oncologists make treatment decisions. A patient’s own tissue is used to create tumors on a chip, which are then used to test various chemotherapy regimens. These chips are currently being evaluated in clinical studies.
“Instead of trying a treatment for six months and finding that it doesn’t work, and then trying another regimen, the tumor may be too far away by then,” Atala said. “We can now try to define the best treatment before the patient receives the first dose.”
Regenerated organs are on the way, Atala said. Technical skin products come onto the market. The next regenerative tissue products will be a little more complex and take on tubular structures. WFIRM regenerated urethra by taking a small sample of tissue from a patient and dilating those cells in a laboratory. These cells colonize a bioresorbable scaffold that can then be implanted in the patient.
Solid organs pose the greatest challenge to regenerative medicine. These organs are made up of many more cells that need to be nourished by the blood supply. WFIRM’s research includes kidneys. A small sample of tissue from a patient is expanded in a laboratory to obtain “kidney units” that can produce urine. These kidney units can then be implanted in the patient. Atala said this research is moving into phase 3 testing for patients with end-stage kidney failure.
When WFIRM began in 2004, scientists didn’t begin research by looking at which patients regenerative medicine technology could help most, Atala said. But now it seems that the greatest area of need seems to be kidney transplant patients.
“As you know, 80% of patients on the transplant waiting list are actually waiting for a kidney,” Atala said. “So if we can dent this population, that would be a great thing.”