Washington: Embryonic stem cells of mice have been transformed into key structures of the inner ear in a breakthrough study.
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.
A research team led by Eri Hashino, Ph.D., Ruth C. Holton Professor of Otolaryngology at Indiana University School of Medicine, reported that by using a three-dimensional cell culture method, they 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.
Dr. Hashino said that 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.
The team 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.
Karl R. Koehler, B.A., the paper`s first author and a graduate student in the medical neuroscience graduate program at the IU School of Medicine, said that the three-dimensional suspension also provided important mechanical cues, such as the tension from the pull of cells on each other.
Koehler said that the 3-D culture allows the cells to self-organize into complex tissues using mechanical cues that are found during embryonic development.
Hashino said that the team was 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.
He said that the team`s 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.
Electrophysiology testing further 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 research is published online in the journal Nature.