Little research has been done on the microenvironment of the cell. Most current knowledge of cell biology comes from studying large populations of cells grown in petri dishes. But that’s much like trying to deduce the habits of a single person based on a bird’s-eye view of New York City. Just as Manhattan can change from rugged to ritzy in a single block, the environment surrounding cells in a live organ can change in the space of micrometers. Understanding that environment is a problem central to the development of cell-based therapies–both those that seek to incorporate cells into artificial devices or engineered tissue and direct therapies using stem cells.
For example, liver cells survive better outside the body if they have as neighbors cells from connective tissue. Bhatia’s lab has been testing specific patterns of cell placement on microfabricated surfaces and has found that certain arrangements of the two types of cells are more stable than others. The researchers are trying to determine what liver cells get from their neighbors: Physical contact? A chemical signal? “We are interested in the dynamics of the cell-cell interaction,” Bhatia says. To help solve this puzzle, postdoctoral fellow Elliot Hui recently developed a device consisting of two tiny interlocking combs that hold cells; with it, the researchers can test how the cells change when they are brought together or held just a few micrometers apart.
These discoveries can help scientists learn the conditions necessary to grow liver cells in devices and, ultimately, to create an artificial liver from cultured cells. Joseph Vacanti, a Harvard Medical School surgeon at Massachusetts General Hospital, is working toward creating artificial organs, including artificial livers. “It remains one of the more challenging problems in the field of tissue engineering,” Vacanti says. “What distinguishes Dr. Bhatia is her ability to successfully combine technologies to help us understand how liver cells work and how to control their function.” Bhatia is also applying some of the same thinking to stem cells, which could potentially be coaxed to become any kind of cell–including liver cells–with the right environmental cues.
Tissue engineering is just one of the clinical applications of Bhatia’s work. Along the way, she realized that the techniques she had developed for studying liver cells could prove equally valuable in screening drugs for liver toxicity. Even the most promising drug can be thwarted if it becomes toxic as it is broken down in the liver. Microtechnology offers a way to array liver cells on patterned surfaces and quickly test the effects of multiple chemicals. The potential of Bhatia’s work to change medicine has garnered her awards such as a five-year Packard Fellowship for promising young scientists and engineers, and Technology Review named her to the 2003 TR100 list of top young innovators. Bhatia’s lab has also won attention for its research in nanotechnology; she and colleagues have worked on harnessing the properties of nanoscale particles to target and treat cancer cells.
Jennifer Elisseeff, PhD ‘99, a fellow HST graduate (and TR100 honoree) and a bioengineer at Johns Hopkins University, says, “What I really like about [Bhatia’s] work is that it sort of defines what we think of as biomedical engineering.” Elisseeff, who focuses on developing new biomaterials from which to construct artificial tissue, adds that Bhatia “develops new devices to study biological problems that have a direct medical application. That’s what we should strive for.” Beyond its immediate uses, Bhatia’s work is drawing attention for a more fundamental reason: it blurs the boundaries between living and artificial systems, which may have far-reaching implications for how we treat disease.