Simple Recipe to Make Sensory Hair Cells in the Ear

Discussion in 'Research News' started by exodus, May 26, 2015.

    1. exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
      Tinnitalkers,

      here s an interesting finding:

      http://medicalxpress.com/news/2015-05-simple-recipe-sensory-hair-cells.html

      Scientists at the Molecular Medicine Institute in Lisbon, Portugal, and at the University College London Ear Institute, United Kingdom, have developed a simple and efficient protocol to generate inner ear hair cells, the cells responsible for our hearing and sense of balance. This study is an important step for the future production of large numbers of these cells for use in cell transplantation therapies or large-scale drug screens. The research has just been published in the scientific journal Development.

      Sensory hair cells located in the inner ear are vital for our sense of hearing and balance. As these cells are unable to regenerate, millions of people worldwide have permanent hearing and balance impairments. Previous studies had already reported the successful generation of hair cells in the lab, but the protocols used were complex and inefficient. To overcome these problems, the team led by Domingos Henrique, whose Neural Development lab is also associated with the Champalimaud Centre for the Unknown in Lisbon, decided to follow a different strategy. "We explored the extensive knowledge on the various regulatory proteins that control hair cell development in the embryo to design an effective combination of three transcription factors able to induce the formation of these cells", said Dr Henrique and Aida Costa, the graduate student involved in the work.

      The team applied this simpler approach to mouse embryonic stem cells in a dish, which have the potential to become any cell type. They were able to convert these cells into hair cells, more successfully and with higher efficiencies than previously reported. Excitingly, when the team added the three players to cells in the ear of a developing chick embryo they were also able to induce the formation of many new hair cells, including in areas where they do not form normally, suggesting that a similar strategy might work in vivo.

      "Hair cells get their name from the bundle of hair-like structures that protrude from the cell. These protrusions have mechanosensitive ion channels that allow hair cells to transform vibrational movements into electrical signals. We observed that the hair cells we produced are also able to develop similar protrusions, but with an immature and disorganized morphology", said the authors. "However, we have some evidence suggesting that functional mechanosensitive ion channels are already present in these cells, and that the genes expressed by normal hair cells and those produced by us in a dish are very similar."

      Future work will focus both on improving this protocol to produce fully mature hair cells, and on applying the method to human cells that can be produced in large quantities. "Producing large numbers of hair cells will allow the development of high-throughput drug screening to discover new compounds that can promote hair cell regeneration. In the long term, they can also be used as a starting point to develop cell replacement therapies that could successfully restore the lost or damaged hair cells in the inner ear", conclude the authors.

      More information: Costa, A., Sanchez-Guardado, L., Juniat, S., Gale, J. E., Daudet, N., Henrique, D. (2015). Generation of sensory hair cells by genetic programming with a combination of transcription factors. Development, 11, 1948-1959. dev.biologists.org/content/142/11/1948
       
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    2. Nucleo

      Nucleo Member Benefactor

      Tinnitus Since:
      02/2011
      Does anyone have access to the full paper?
       
    3. AUTHOR
      AUTHOR
      exodus
      Cold

      exodus Member

      Tinnitus Since:
      05/2008
      i ve tried but got paywall
      just was able to read the name of the 3 molecules they are using:

      Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
       
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    4. joejunior

      joejunior Member

      Tinnitus Since:
      05/2001
      Here is more:
      http://medicalxpress.com/news/2015-05-inner-ear-hair-cells-advances-deafness.html#inlRlv

      This is very encouraging, not only have they created the 'parts list' but it is publicly available. One of the issues in private medical research is lack of sharing of data, and patenting of genes etc, this is a real roadblock to research. So publicly sharing the data , allows scientists all around the world to access it, which accelerates the research.

      "Now we have a panel of all the genes that are involved in hair cell development," Scheffer said.

      Scheffer and Corey deposited their data in a publicly available database that Shen established three years ago. The Shared Harvard Inner Ear Laboratory Database, or SHIELD, holds gene expression data integrated with comprehensive annotation, including potential locations for deafness genes. Scientists from around the world access the data more than 400 times a day.

      Some scientists interested in the molecular biology of hearing and deafness can use SHIELD to identify new deafness genes, which may lead to specific gene therapies. Others want to know what makes a hair cell a hair cell, so they can find a way to make surrounding cells in the inner ear turn into hair cells. These cells do not normally divide, so once they are lost, the only hope is to somehow induce them to divide or to turn neighboring cells into hair cells.
       
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    5. joejunior

      joejunior Member

      Tinnitus Since:
      05/2001
    6. Sharpfire
      No Mood

      Sharpfire Member

      Location:
      London
      Tinnitus Since:
      12/2014
      Cause of Tinnitus:
      Unknown
      I have a login that lets me access the full paper, but it's too large to attach here. I can copy & paste parts if anyone wants something specific.
       
    7. Nucleo

      Nucleo Member Benefactor

      Tinnitus Since:
      02/2011
      @Sharpfire I see from your profile pic you seem to be working in a lab. What kind of research do you do?
       
    8. Sharpfire
      No Mood

      Sharpfire Member

      Location:
      London
      Tinnitus Since:
      12/2014
      Cause of Tinnitus:
      Unknown
      It's an old pic, I'll probs change it soon. It's from when I interned at a neurosceicne lab in University College London (UCL) (also known as the place where autifony trials are happening). I'm not a researcher but I'm considering becoming one/working for a large pharma. The last time I worked in a lab was during a uni research project (I'm about to graduate in biology/biomed - specialised in cell biology).
       
    9. Nucleo

      Nucleo Member Benefactor

      Tinnitus Since:
      02/2011
      Ahh ok. I'm a researcher myself but very far from Tinnitus research or any life sciences for that matter. I've considered switching careers to T research but that would probably require more schooling. My last biology/biochemistry courses were several years ago :(
       
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