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Liu, Wei
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Publications (10 of 34) Show all publications
Senn, P., Roccio, M., Hahnewald, S., Frick, C., Kwiatkowska, M., Ishikawa, M., . . . Loewenheim, H. (2017). NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons. Paper presented at 14th International Conference on Cochlear Implants and other Implantable Auditory Technologies, MAY 11-14, 2016, Toronto, CANADA. Otology and Neurotology, 38(8), E224-E231.
Open this publication in new window or tab >>NANOCI-Nanotechnology Based Cochlear Implant With Gapless Interface to Auditory Neurons
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2017 (English)In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 38, no 8, E224-E231 p.Article in journal (Refereed) Published
Abstract [en]

Cochlear implants (CI) restore functional hearing in the majority of deaf patients. Despite the tremendous success of these devices, some limitations remain. The bottleneck for optimal electrical stimulation with CI is caused by the anatomical gap between the electrode array and the auditory neurons in the inner ear. As a consequence, current devices are limited through 1) low frequency resolution, hence suboptimal sound quality and 2), large stimulation currents, hence high energy consumption (responsible for significant battery costs and for impeding the development of fully implantable systems). A recently completed, multinational and interdisciplinary project called NANOCI aimed at overcoming current limitations by creating a gapless interface between auditory nerve fibers and the cochlear implant electrode array. This ambitious goal was achieved in vivo by neurotrophin-induced attraction of neurites through an intra-cochlear gel-nanomatrix onto a modified nanoCI electrode array located in the scala tympani of deafened guinea pigs. Functionally, the gapless interface led to lower stimulation thresholds and a larger dynamic range in vivo, and to reduced stimulation energy requirement (up to fivefold) in an in vitro model using auditory neurons cultured on multi-electrode arrays. In conclusion, the NANOCI project yielded proof of concept that a gapless interface between auditory neurons and cochlear implant electrode arrays is feasible. These findings may be of relevance for the development of future CI systems with better sound quality and performance and lower energy consumption. The present overview/review paper summarizes the NANOCI project history and highlights achievements of the individual work packages.

Keyword
Auditory nerve regeneration, BDNF, Cochlear implant, Gapless interface, Guinea pig, Hearing loss, Hydrogel, Multi-electrode array, Neuron-electrode interface
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-335874 (URN)10.1097/MAO.0000000000001439 (DOI)000411032100003 ()28806330 (PubMedID)
Conference
14th International Conference on Cochlear Implants and other Implantable Auditory Technologies, MAY 11-14, 2016, Toronto, CANADA
Funder
EU, European Research Council, 281056
Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2017-12-14Bibliographically approved
Liu, W., Schrott-Fischer, A., Glueckert, R., Benav, H. & Rask-Andersen, H. (2017). The Human "Cochlear Battery" - Claudin-11 Barrier and Ion Transport Proteins in the Lateral Wall of the Cochlea. Frontiers in Molecular Neuroscience, 10, Article ID 239.
Open this publication in new window or tab >>The Human "Cochlear Battery" - Claudin-11 Barrier and Ion Transport Proteins in the Lateral Wall of the Cochlea
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2017 (English)In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, 239Article in journal (Refereed) Published
Abstract [en]

Background: The cochlea produces an electric field potential essential for hair cell transduction and hearing. This biological "battery" is situated in the lateral wall of the cochlea and contains molecular machinery that secretes and recycles K+ ions. Its functioning depends on junctional proteins that restrict the para-cellular escape of ions. The tight junction protein Claudin-11 has been found to be one of the major constituents of this barrier that maintains ion gradients (Gow et al., 2004; Kitajiri et al., 2004a). We are the first to elucidate the human Claudin-11 framework and the associated ion transport machinery using super-resolution fluorescence illumination microscopy (SR-SIM). Methods: Archival cochleae obtained during meningioma surgery were used for SR-SIM together with transmission electron microscopy after ethical consent. Results: Claudin-11-expressing cells formed parallel tight junction lamellae that insulated the epithelial syncytium of the stria vascularis and extended to the suprastrial region. Intercellular gap junctions were found between the barrier cells and fibrocytes. Conclusion: Transmission electron microscopy, confocal microscopy and SR-SIM revealed exclusive cell specialization in the various subdomains of the lateral wall of the human cochlea. The Claudin-11-expressing cells exhibited both conductor and isolator characteristics, and these micro-porous separators may selectively mediate the movement of charged units to the intrastrial space in a manner that is analogous to a conventional electrochemical "battery." The function and relevance of this battery for the development of inner ear disease are discussed.

Keyword
human, cochlea, stria vascularis, spiral ligament, Claudin-11, structured illumination microscopy
National Category
Neurosciences Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-332662 (URN)10.3389/fnmol.2017.00239 (DOI)000407621000001 ()28848383 (PubMedID)
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2018-01-13Bibliographically approved
Hellberg, V., Gahm, C., Ehrsson, H., Liu, W., Rask-Andersen, H. & Laurell, G. (2016). In Response to Immunohistochemical Localization of OCT2 in the Cochlea of Various Species [Letter to the editor]. The Laryngoscope, 126(6), E232-E232.
Open this publication in new window or tab >>In Response to Immunohistochemical Localization of OCT2 in the Cochlea of Various Species
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2016 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 6, E232-E232 p.Article in journal, Letter (Refereed) Published
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-301136 (URN)10.1002/lary.25879 (DOI)000379980200009 ()26864569 (PubMedID)
Available from: 2016-08-22 Created: 2016-08-18 Last updated: 2017-11-28Bibliographically approved
Cai, Y., Edin, F., Jin, Z., Alexsson, A., Gudjonsson, O., Liu, W., . . . Li, H. (2016). Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond. Acta Biomaterialia, 31, 211-220.
Open this publication in new window or tab >>Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond
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2016 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, 211-220 p.Article in journal (Refereed) Published
Abstract [en]

Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

National Category
Medical Materials Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-266956 (URN)10.1016/j.actbio.2015.11.021 (DOI)000370086100019 ()26593784 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 603029
Available from: 2015-11-14 Created: 2015-11-14 Last updated: 2017-12-01Bibliographically approved
Liu, W., Edin, F., Blom, H., Magnusson, P., Schrott-Fischer, A., Glueckert, R., . . . Rask-Andersen, H. (2016). Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man. Cell and Tissue Research, 365(1), 13-27.
Open this publication in new window or tab >>Super-resolution structured illumination fluorescence microscopy of the lateral wall of the cochlea: the Connexin26/30 proteins are separately expressed in man
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2016 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 365, no 1, 13-27 p.Article in journal (Refereed) Published
Abstract [en]

Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.

Keyword
Human cochlea, Connexin (as elsewhere) 26/30, Structured illumination microscopy
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-299834 (URN)10.1007/s00441-016-2359-0 (DOI)000378877600003 ()26941236 (PubMedID)
Available from: 2016-07-29 Created: 2016-07-28 Last updated: 2018-01-10Bibliographically approved
Hayashi, H., Edin, F., Li, H., Liu, W. & Rask-Andersen, H. (2016). The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling. Brain Research, 1652, 195-203.
Open this publication in new window or tab >>The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling
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2016 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1652, 195-203 p.Article in journal (Refereed) Published
Abstract [en]

Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca(2+) signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca(2+) channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca(2+) channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca(2+) signaling.

Keyword
Pulsed electric field, Human neural progenitor cell, Electrotactic migration, Intracellular calcium signaling, Time-lapse video microscopy
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-310911 (URN)10.1016/j.brainres.2016.09.043 (DOI)000388059700023 ()27746154 (PubMedID)
Funder
EU, European Research Council, 281056 603029
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2017-11-29Bibliographically approved
Guo, R., Zhang, H., Chen, W., Zhu, X., Liu, W. & Rask-Andersen, H. (2016). The inferior cochlear vein: surgical aspects in cochlear implantation. European Archives of Oto-Rhino-Laryngology, 273(2), 355-361.
Open this publication in new window or tab >>The inferior cochlear vein: surgical aspects in cochlear implantation
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2016 (English)In: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 273, no 2, 355-361 p.Article in journal (Refereed) Published
Abstract [en]

The patency of the inferior cochlear vein (ICV) may be challenged in cochlear implantation (CI) due to its location near the round window (RW). This may be essential to consider during selection of different trajectories for electrode insertion aiming at preserving residual hearing. Venous blood from the human cochlea is drained through the ICV. The vein also drains blood from the modiolus containing the spiral ganglion neurons. Surgical interference with this vein could cause neural damage influencing CI outcome. We analyzed the topographical relationship between the RW and ICV bony channel and cochlear aqueduct (CA) from a surgical standpoint. Archival human temporal bones were further microdissected to visualize the CA and its accessory canals (AC1 and AC2). This was combined with examinations of plastic and silicone molds of the human labyrinth. Metric analyses were made using photo stereomicroscopy documenting the proximal portion of the AC1, the internal aperture of the CA and the RW. The mean distance between the AC1 and the anterior rim of the RW was 0.81 mm in bone specimens and 0.67 mm assessed in corrosion casts. The AC1 runs from the floor of the scala tympani through the otic capsule passing parallel to the CA to the posterior cranial fossa. The mean distance between the CA and AC1 canal was 0.31 and 0.25 mm, respectively.

Keyword
Cochlea; Human; Inferior cochlear vein; Cochlear implants
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-265774 (URN)10.1007/s00405-015-3549-1 (DOI)000368990700013 ()25700831 (PubMedID)
Funder
Swedish Research Council, A0290401Swedish Research Council, A0290402EU, FP7, Seventh Framework Programme, 281056
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-12-01Bibliographically approved
Rask-Andersen, H. & Liu, W. (2015). Auditory nerve preservation and regeneration in man: relevance for cochlear implantation. Neural Regeneration Research, 10(5), 710-712.
Open this publication in new window or tab >>Auditory nerve preservation and regeneration in man: relevance for cochlear implantation
2015 (English)In: Neural Regeneration Research, ISSN 1673-5374, E-ISSN 1876-7958, Vol. 10, no 5, 710-712 p.Article in journal, Editorial material (Other academic) Published
National Category
Neurosciences Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-258572 (URN)10.4103/1673-5374.156963 (DOI)000355964400013 ()26109941 (PubMedID)
Available from: 2015-07-16 Created: 2015-07-15 Last updated: 2018-01-11Bibliographically approved
Hellberg, V., Gahm, C., Liu, W., Ehrsson, H., Rask-Andersen, H. & Laurell, G. (2015). Immunohistochemical localization of OCT2 in the cochlea of various species. The Laryngoscope, 125(9), E320-E325.
Open this publication in new window or tab >>Immunohistochemical localization of OCT2 in the cochlea of various species
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2015 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 125, no 9, E320-E325 p.Article in journal (Refereed) Published
Abstract [en]

ObjectiveTo locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2. Study DesignImmunohistochemical and in vivo study. MethodsSections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry. ResultsOrganic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin. ConclusionsThe localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea. Level of EvidenceN/A. Laryngoscope, 125:E320-E325, 2015

Keyword
Cisplatin, ototoxicity, OCT2, phenformin
National Category
Surgery Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-262970 (URN)10.1002/lary.25304 (DOI)000360231700005 ()25892279 (PubMedID)
Available from: 2015-09-23 Created: 2015-09-23 Last updated: 2017-12-01Bibliographically approved
Liu, W., Atturo, F., Aldaya, R., Santi, P., Cureoglu, S., Obwegeser, S., . . . Rask-Andersen, H. (2015). Macromolecular organization and fine structure of the human basilar membrane - RELEVANCE for cochlear implantation. Cell and Tissue Research, 360(2), 245-262.
Open this publication in new window or tab >>Macromolecular organization and fine structure of the human basilar membrane - RELEVANCE for cochlear implantation
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2015 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 360, no 2, 245-262 p.Article in journal (Refereed) Published
Abstract [en]

Introduction Cochlear micromechanics and frequency tuning depend on the macromolecular organization of the basilar membrane (BM), which is still unclear in man. Novel techniques in cochlear implantation (CI) motivate further analyses of the BM. Materials and methods Normal cochleae from patients undergoing removal of life-threatening petro-clival meningioma and an autopsy specimen from a normal human were used. Laser-confocal microscopy, high resolution scanning (SEM) and transmission electronmicroscopy (TEM) were carried out in combination. In addition, one human temporal bone was decellularized and investigated by SEM. Results The human BM consisted in four separate layers: (1) epithelial basement membrane positive for laminin-beta 2 andcollagen IV, (2) BM Bproper boolean AND composed of radial fibers expressing collagen II and XI, (3) layer of collagen IV and (4) tympanic covering layer (TCL) expressing collagen IV, fibronectin and integrin. BM thickness varied both radially and longitudinally (mean 0.55-1.16 mu m). BM was thinnest near the OHC region and laterally. Conclusions There are several important similarities and differences between the morphology of the BM in humans and animals. Unlike in animals, it does not contain a distinct pars tecta (arcuate) and pectinata. Its width increases and thickness decreases as it travels apically in the cochlea. Findings show that the human BM is thinnest and probably most vibration-sensitive at the outer pillar feet/Deiter cells at the OHCs. The inner pillar and IHCs seem situated on a fairly rigid part of the BM. The gradient design of the BM suggests that its vulnerability increases apical wards when performing hearing preservation CI surgery.

Keyword
Basilar membrane, Human, Collagen II, Ultrastructure, Cochlear implant
National Category
Otorhinolaryngology Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-257031 (URN)10.1007/s00441-014-2098-z (DOI)000355567700005 ()25663274 (PubMedID)
Available from: 2015-06-30 Created: 2015-06-29 Last updated: 2017-12-04Bibliographically approved
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