A team of researchers at Indiana University, using a three-dimensional cell culture method, has successfully transformed mouse embryonic stem cells into key structures of the inner ear.
In the study, reported in the journal Nature, Prof Eri Hashino and his colleagues were able to coax stem cells to develop into inner-ear sensory epithelia – containing hair cells, supporting cells and neurons – that detect sound, head movements and gravity.
“Previous attempts to ‘grow’ inner-ear hair cells in standard cell culture systems have worked poorly in part because necessary cues to develop hair bundles are lacking in the flat cell-culture dish. But the team determined that the cells needed to be suspended as aggregates in a specialized culture medium, which provided an environment more like that found in the body during early development,” Dr Hashino said.
The scientists mimicked the early development process with a precisely timed use of several small molecules that prompted the stem cells to differentiate, from one stage to the next, into precursors of the inner ear.
“But the 3D suspension also provided important mechanical cues, such as the tension from the pull of cells on each other,” said study first author Dr Karl Koehler.
“The 3D culture allows the cells to self-organize into complex tissues using mechanical cues that are found during embryonic development.”
“We were surprised to see that once stem cells are guided to become inner-ear precursors and placed in 3-D culture, these cells behave as if they knew not only how to become different cell types in the inner ear, but also how to self-organize into a pattern remarkably similar to the native inner ear. Our initial goal was to make inner-ear precursors in culture, but when we did testing we found thousands of hair cells in a culture dish,” Dr Hashino added.
Testing proved that those hair cells generated from stem cells were functional, and were the type that sense gravity and motion. Moreover, neurons like those that normally link the inner-ear cells to the brain had also developed in the cell culture and were connected to the hair cells.
The discovery provides new insights into the sensory organ’s developmental process and sets the stage for laboratory models of disease, drug discovery and potential treatments for hearing loss and balance disorders.
Bibliographic information: Karl Koehler et al. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature, published online July10, 2013; doi: 10.1038/nature12298