Professor Marcelo N. Rivolta
Professor of Sensory Stem Cell Biology
Room: C226 Alfred Denny building
Brief career history
Deafness is a major public health issue worldwide, with more than 3 million people in the UK alone enduring a moderate to profound hearing loss. The Rivolta laboratory is dedicated to study the biology and behaviour of auditory stem cells (primarily human) and to explore their potential to regenerate the damaged inner ear.
Invited to give numerous seminars, opening and plenary lectures.
In the media
Regenerative therapies for hearing loss: The development and use of human stem cells
Hearing loss has substantial personal, social and economic implications. It is most commonly caused by damage to the sensory hair cells and/or the auditory neurons in the cochlea. One possible therapeutic path would be to use otic progenitors generated in vitro to functionally replace the damaged cells.
Our group has made key advances developing stem cell technologies into a potentially viable therapy. We isolated a population of stem cells from the human fetal cochlea, and we have developed robust protocols to drive otic differentiation from human pluripotent stem cells. We also have established the proof of concept that hESC-derived otic progenitors can repair the damaged cochlea. We demonstrated that transplanted cells can graft into an animal model of auditory neuropathy, and elicit functional recovery as measured by auditory brainstem thresholds.
In an integrative regenerative medicine strategy, we are now exploring the combination of stem cells with cochlear implants, aiming to develop a true bionic implant. This device should conceptually combine stem cells with stimulatory electrodes. For this we are developing animal models of cell transplantation and implantation. On a parallel strategy, we are also using stem cells to develop in vitro platforms that would facilitate drug discovery and analysis.
We have several collaborations with industry and academia, within the UK as well as worldwide. We are part of Otostem, an international consortium with partners in Stanford, Harvard, Geneva, Uppsala, Tübigen and Marseille.
Undergraduate and postgraduate taught modules
PhD Studentship starting October 2017
Title: Exploring re-innervation and synaptogenesis between human stem cell-derived auditory neurons and inner hair cells: A therapeutic model for ‘hidden hearing loss’
Supervisors: Professor Marcelo Rivolta and Dr Stuart Johnson
Finding: Competition funded project European/UK students only.
Loud noise exposure and aging lead to the permanent loss of afferent synaptic contacts to the primary sensory inner hair cells (IHCs) in the cochlea, whilst causing only a temporary or undetectable hearing threshold shift. This ‘synaptopathy’ reduces IHC afferent innervation by up to 50% leaving an individual unable to detect sounds in a noisy environment and experiencing difficulties with speech discrimination and intelligibility. Since the hearing thresholds are unaltered, it is difficult to detect the condition using conventional hearing tests, hence it is named ‘hidden hearing loss’. The loss of synaptic contacts is also thought to underlie primary neural degeneration in acquired hearing loss and aging.
The causative mechanisms underlying cochlear synaptopathy are not well understood. While it is believed to be a result of the toxic effects of overstimulating these fibres, it is not known whether there are any changes in the properties of the IHCs that lead to axonal retraction or, conversely, whether there are any IHC changes that result from it.
We have previously shown that human embryonic stem cell-derived spiral ganglion neurons (SGNs) can be transplanted into an animal model and establish synaptic connections and recovery of function. To address the specific role of the afferent fibres the student will learn to co-culture the adult gerbil organ of Corti with hESC-derived SGNs to see if the IHC properties have changed in order to attract new fibres and/or whether new synaptic innervation of the hair cells can restore their mature phenotype.
This study will allow us to understand the chain of events that lead to the ‘de-differentiation’ of IHCs in culture and whether it can be reversed by re-innervation from stem cell-derived SGNs. The advantages of using the mature organotypic culture as a model system to study IHC and afferent fibre synaptopathy, and cochlear plasticity in general, are that the conditions can be easily manipulated whilst monitoring the characteristics of the IHCs and afferent fibres throughout.
Keywords: Biophysics, Cell Biology / Development, Molecular Biology, Neuroscience / Neurology, Biophysics
Further information about this project can be found on our PhD Opportunities page:
- Boddy SL, Chen W, Romero-Guevara R, Kottam L, Bellantuono I & Rivolta MN (2012) Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells.. Regen Med, 7(6), 757-767.
- Chen W, Jongkamonwiwat N, Abbas L, Eshtan SJ, Johnson SL, Kuhn S, Milo M, Thurlow JK, Andrews PW, Marcotti W, Moore HD & Rivolta MN (2012) Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.. Nature, 490(7419), 278-282. View this article in WRRO
- Chen W, Johnson SL, Marcotti W, Andrews PW, Moore HD & Rivolta MN (2009) Human fetal auditory stem cells can be expanded in vitro and differentiate into functional auditory neurons and hair cell-like cells.. Stem Cells, 27(5), 1196-1204.