Imagine being able to grow part of an organ in a lab – and then run tests on its functioning in order to truly understand how best to treat a particular condition. Rather than use human subjects to test new therapies, which involves costly and complex pharmaceutical quality control protocols, researchers could develop customized treatments using genetically engineered samples.
Scientists from Harvard’s Wyss Institute, Boston Children’s Hospital, and the Harvard School of Engineering and Applied Sciences have collaborated to revolutionize clinical research with new organ-on-a-chip technology. Using patient stem cells, the team actually engineered part of a heart. The organ was built to include a perfect replica of the patient’s genetic disorder – a rare disease called Barth syndrome that affects mostly boys and impacts heart and skeletal muscle function.
Genome editing leads to a cure
The researchers grew samples of the patient’s stem cells on dishes lined with extracellular material that mimicked their natural environment in the body. Essentially, they tricked the cells to fuse together into a real human heart. Then, using a new process called genome editing, the scientists mutated a particular gene galled TAZ (Tavazzin) – a mutation that causes the onset of Barth syndrome. The engineered tissue demonstrated the same weaknesses as the patient’s heart – weaknesses the team corrected by applying their newly developed product. It was the first time a genetic heart disease was corrected using a lab-based tissue model.
Seeing the big picture
Organ-on-a-chip pioneer, Kevin Kit Parker PhD emphasizes the technology’s importance saying, “You don’t really understand the meaning of a single cell’s genetic mutation until you build a huge chunk of organ and see how it functions or doesn’t function…Being able to model the disease from a single cell all the way up to heart tissue, I think that’s a big advance.” Getting a clearer, larger picture of how disease impacts tissues and the efficacy of test treatments is central to our ability to create customized remedies – which as students in pharmaceutical courses understand is the future of targeted medicine.
Saving animal test subjects
Up until now, bone marrow could only be studied in living animals. The Harvard team has applied its organ engineering science to the development of fully functional bone marrow in the lab. Not only does this advance save the lives of test subjects, it provides a much-needed means of evaluating the efficacy or toxicity of new drugs on whole bone marrow. And what’s more, bone-marrow-on-a-chip could help maintain cancer patients’ own marrow while undergoing radiation and chemotherapy.
In addition to the heart and bone marrow-on-chips, the Harvard team has engineered living lung, gut, and kidney models and has more organ projects in the works.
How do you think genetically engineered and modified organs will impact clinical research most over the coming decade?