Dr. Heller discusses a recent paper from the Heller Lab, published in the journal Stem Cells & Development, and the work worldwide to regenerate human inner ear hair cells for the restoration of hearing:
The start to 2014 has been very exciting with many new advances to be published by our laboratory, but also by many of my colleagues. Of course, each university will try to publicize these successes by generating lots of press, which seems to be the name of the game nowadays. I admit that this is tremendously confusing for patients and parents of children with hearing loss and it can be frustrating because it could raise the hope that cures are just around the corner. Unfortunately, there is still lots of work to be done.
This said, I would also like to play the drums also a little bit by reporting a small but quite important paper by our own group that just got published a couple of days ago in the journal Stem Cells & Development. There has been no glorifying press release about this story, mainly because it is not in a flashy journal but also because it reports lots of limitations of existing stem cell technology, particularly when it comes to generation of human inner ear cell types.
Some readers might remember a 2012 Nature publication by a research group from Sheffield University, in the UK, reporting the restoration of some auditory function in laboratory animals with damaged auditory nerve by transplantation of human embryonic stem cell-derived nerve cells. Buried in this paper was also a figure where the authors reported generation of, not very convincing looking, human sensory hair cells. Our laboratory has also been working on generating human hair cells for almost 8 years now. When the 2012 Nature paper came out, my postdoc Mohammad Ronaghi asked me why “his” hair cells (which looked a little more convincing than the published images) were not ready for publication.
Mohammad’s cells indeed were quite pretty and they were generated by coaxing human embryonic stem cells to show many signs of an inner ear phenotype. Despite this peer-pressure, we decided to spend more energy on the project because we wanted a result that would be highly convincing – perhaps even by using the cells to restore auditory function in a sensory hair cell loss animal model. Now it is 2014, and despite some additional steps, we did not reach this goal. What we learned are several limitations to the use of human stem cell-generated inner ear cells that undoubtedly require lots of additional work in the upcoming years. This work is difficult – we knew this before, but man, it is really difficult! We decided to publish our findings at this point because we wanted to let other researchers know about our experience. On the other hand, the results that we published are probably the best looking stem cell-generated human hair cell-like cells that have been generated thus far.
In my mind, our publication is not the endpoint, but rather the beginning of multiple novel approaches to address the existing limitations. It is a short paper but the product of a massive amount of work over many years. Somehow, these are difficult papers for a laboratory, frustrating for the postdocs doing the work, and not the kind of publication that carry fame. But in my mind, this is honest and hard work by the postdocs, students, and staff of my group and I highly appreciate their effort and sacrifices. It is clear that much more work is needed, but on the other hand, the story needed to be told now so that new approaches and new directions can be tested. It is a little like clearing the air, reshuffling, and taking off with new energy.
Perhaps the best news for the human approach comes from the European Union (surprise!). Our laboratory is part of a consortium funded by the European Union to investigate in collaborative manner human stem cell applications for the treatment of hearing loss (http://www.otostem.org). My hope for this concerted effort is that research will be faster, and that groups collaborate instead of compete with each other. So far so good – we just had our kickoff meeting and first coordination meeting to get the planned research started. Several of the limitations that hamper human stem cell applications are being addressed by this group effort, which makes me hopeful.