According to the World Health Organization, approximately 360 million people suffer from hearing impairment. Noise-induced cell death is the primary cause, and once hair cells are gone, they don’t come back – at least in humans anyway. Birds and amphibians are able to regenerate their sensory hair cells, and the human intestinal lining regenerates every 4 to 5 days. These facts prompted Jeff Karp, Associate Professor of Medicine at Brigham and Women’s Hospital, and his team to ask a question: what is the biological mechanism that prevents mammalian inner ear progenitor cells from dividing and forming new hair cells?
“In regenerative tissues, a progenitor cell will divide before becoming a differentiated cell type,” says Karp. “Mammalian inner ear cochlear progenitor cells lose this ability after fetal development has completed.” This means that drug discovery for the inner ear is limited by the inability to acquire enough primary cells to explore drug targets. But Karp and his colleagues have developed a way to create large populations of progenitor cells and hair cells, via a method they call “Progenitor Cell Activation." In a recent study (1), the team identified a combination of small molecules that enable inner ear progenitor cells to form large pure colonies, which can be subsequently converted into fully developed hair cells in high yield. These molecules were effective for inner ear progenitor cells isolated from young mice, old mice, monkeys, and humans. “With the same molecules, we were able to regenerate lost hair cells when applied to isolated cochleae that had their hair cells destroyed,” says Will McLean, one of the co-lead authors of the paper, and Vice President of Biology and Regenerative Medicine at Frequency Therapeutics – a company set up in 2015 by Karp and Robert Langer, David H. Koch Institute Professor at Massachusetts Institute of Technology, to develop disease modifying therapeutics using Progenitor Cell Activation. “Our next step is to bring this proprietary platform approach into clinical testing, which we plan to do within the next 18 months after the required toxicology and safety studies,” says Karp.
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References
- W J McLean et al., “Clonal expansion of Lgr5-positive cells from mammalian cochlea and high-purity generation of sensory hair cells”, Cell Reports, 18, 8, 1917-1929 (2017). PMID: 28228258.
