Protektion und Regeneration des Innenohrs

Das Labor der Gruppe „Protektion und Regeneration des Innenohrs“ der Abteilung für Hals-Nasen-Ohren-Heilkunde der MHH befindet sich im NIFE. Eine enge Zusammenarbeit zwischen Klinikern und Wissenschaftlern zielt darauf ab, neuartige Therapiestrategien für das Innenohr zu entwickeln, die zu einer schnellen Translation in die Klinik führen. Die Hauptforschung konzentriert sich auf zellbasierte Ansätze zur Freisetzung von Proteinen und Arzneimitteln über längere Zeiträume an das Innenohr.

Forschung

Hörverlust ist eine der häufigsten neurodegenerativen Erkrankungen, von der jeder sechste Europäer betroffen ist (HEAR IT.ORG 2019). Trotz umfangreicher Investitionen in die medizinische Forschung entstehen jedes Jahr nur eine Handvoll neuer therapeutischer Produkte. Bisher gibt es keine Klasse von Innenohrmedikamenten zur Vorbeugung von Innenohrschäden oder zur Behandlung von Hörverlust und damit verbundenen Erkrankungen.

Die Wiederherstellung des Hörvermögens basiert auf technischen Geräten, entweder mit Hörgeräten zur Schallverstärkung oder mit Cochlea-Implantaten zur direkten elektrischen Stimulation der Spiralganglienneurone. Obwohl Cochlea-Implantate bei vielen Patienten die Schallwahrnehmung wiederherstellen, reicht die Cochlea-Implantation für das Sprachverständnis bei einer großen Anzahl von Patienten nicht aus, wodurch der notwendige Verbesserungsbedarf betont wird. Die Elektroden-Arrays des Cochlea-Implantats werden in das Innenohr eingeführt und bieten dabei den Zugang zur ansonsten unzugänglichen Cochlea. Damit sind sowohl diagnostische Probenentnahmen von Innenohrflüssigkeiten (Perilymphe) als auch die lokale intracochleäre Verabreichung von Therapeutika möglich.

Die Kombination aus Grundlagenforschung und klinischer Forschung innerhalb unserer Gruppe zielt darauf ab, neuartige zellbasierte Therapiestrategien für das Innenohr zu entwickeln, die zu einer schnellen Translation in die Klinik führen. Es gibt mehrere Ansätze zur Behandlung von Innenohrerkrankungen, die die Zukunft hörgeschädigter Menschen und insbesondere von Anwendern des Cochlea-Implantats verändern werden. Die Analyse von cochleären Perilympheproben ermöglicht die Charakterisierung des molekularen Profils von Cochlea-Implantat-Patienten und hilft bei der Identifizierung neuer therapeutischer Ziele. Zellbasierte Ansätze zeigen eine Vielzahl von Vorteilen, einschließlich der Möglichkeit, komplexe Proteine und Arzneimittel über längere Zeiträume abzugeben.

Ein Schlüsselfaktor bei der Entwicklung der Zelltherapie ist der Ursprung der Zellen. Hier konzentrieren wir uns vor allem auf autologe (körpereigene) Zellen und Zellprodukte die den Schutz und die Regeneration des Innenohrs bewirken und die Leistung, die mit einem Cochlea-Implantat erzielt werden kann, verbessern. Derzeit werden Biohybridelektroden (ROEMER ET AL. 2016), die in unserer Forschungsgruppe entwickelt wurden, routinemäßig in unserer Klinik implantiert, um Fremdkörperreaktionen und Entzündungen zu reduzieren. Aus dem Knochenmark stammende humane mesenchymale Stromazellen (MSC) werden dabei als autologe Zellquelle für zellbasierte Systeme verwendet. Diese Zellen setzen immunmodulative Faktoren frei, um Entzündungen auszugleichen, und haben eine hoch schützende Wirkung auf cochleäre Zellen.

Wir nehmen an, dass die therapeutischen Wirkungen von MSC hauptsächlich mit ihrer Sekretion von biologisch aktiven Faktoren und insbesondere mit extrazellulären Vesikeln (EVs) zusammenhängen und nicht mit ihren Differenzierungseigenschaften. Die nanogroßen EVs werden von fast allen Zelltypen freigesetzt und enthalten hochaktive Biomoleküle aus ihren Elternzellen: Proteine, verschiedene Nukleinsäuren, Kohlenhydrate, Lipide und Metaboliten. Durch die geringe Immunogenität und Toxizität stellen eine lange Halbwertszeit und die Fähigkeit, die Blut-Hirn-Schranke zu überwinden, einen vielversprechenden Ansatz dar, um eine Vielzahl verschiedener Faktoren zu verabreichen, die als Therapeutika wirken. Im Hinblick auf die zukünftige klinische Anwendung untersuchten wir MSC-EVs aus der menschlichen Nabelschnur, die ein erhöhtes Überleben von cochleären Neuronen in vitro und den Schutz von Haarzellen sowie des Hörvermögens vor Lärmtrauma in vivo zeigten (WARNECKE ET AL. 2020).

In diesem Zusammenhang wird eine genetische Veränderung sowie eine Strukturierung der Implantatoberfläche durchgeführt, um die Differenzierung von MSC zu induzieren und zu kontrollieren. Darüber hinaus werden die endogenen Regenerationskapazitäten des Innenohrs in Cochlea-spezifischen in-vitro Zellkultursystemen untersucht, einschließlich mikrochirurgischer Techniken zur Vorbereitung des Innenohrs und verschiedener in-vivo Modelle (Lärmtrauma, Fibrose, Erhalt von Resthörvermögen). Stammzelltechnologien, Molekularbiologie, elektrophysiologische Messungen sowie moderne bildgebende Verfahren werden in einem interdisziplinären Ansatz kombiniert, um unsere geplanten Ziele zu verfolgen.

GRUPPENLEITUNG
Prof. Dr.
Athanasia Warnecke
Klinik für Hals-Nasen-Ohrenheilkunde
Dr. rer. nat.
Jennifer Harre
Post Doc
PhD
Odett Kaiser
Post Doc
Dr. med. vet.
Susanne Sasse
Post Doc
Dr. rer. nat.
Heike Schmitt
Post Doc
Dr. rer. nat.
Melanie Steffens
Post Doc
Dahua Wang
Doktorand

Publikationen

• Van Dieken A., Staecker H., Schmitt H., Harre J., Pich A., Roßberg W., Lenarz T., Durisin M., Warnecke A. Bioinformatic Analysis of the Perilymph Proteome to Generate a Human Protein Atlas  Front. Cell Dev. Biol., 28 April 2022. Doi: 10.3389/fcell.2022.847157

• Pietsch M, Schurzig D, Salcher R, Warnecke A, Erfurt P, Lenarz T, Kral A. Variations in microanatomy of the human modiolus require individualized cochlear implantation. Sci Rep. 2022 Mar 23;12(1):5047. doi: 10.1038/s41598-022-08731-x

• Durisin M, Krüger C, Pich A, Warnecke A, Steffens M, Zeilinger C, Lenarz T, Prenzler N, Schmitt H.  Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance? One. 2022 Mar 3;17(3):e0263765. doi: 10.1371/journal.pone.0263765. eCollection 2022.

• Schulze J, Staecker H, Wedekind D, Lenarz T, Warnecke A. Expression pattern of brain-derived neurotrophic factor and its associated receptors: Implications for exogenous neurotrophin application. Hear Res. 2022 Jan;413:108098. doi: 10.1016/j.heares.2020.108098. Epub 2020 Oct 21

• Wille I, Harre J, Oehmichen S, Lindemann M, Menzel H, Ehlert N, Lenarz T, Warnecke A, Behrens P. Development of Neuronal Guidance Fibers for Stimulating Electrodes: Basic Construction and Delivery of a Growth Factor. Front Bioeng Biotechnol. 2022 Jan 24;10:776890. doi: 10.3389/fbioe.2022.776890. eCollection 2022

 

2021
Warnecke A., Prenzler N., Harre J., Köhl U., Gärtner L., Lenarz T., Laner-Plamberger S., Wietzorrek G., Staecker H., Lassacher T., Hollerweger J., Gimona M., Rohde E. First-in-human intracochlear application of 1 extracellular vesicle-enriched secretome from umbilical cord mesenchymal stromal cells in a patient with Menière’s disease during cochlear implantation. (https://onlinelibrary.wiley.com/doi/10.1002/jev2.12094) J Extracell Vesicles. 2021 Jun 04; 10:e12094. doi: 10.1002/jev2.12094.

Shew M, Wichova H, Warnecke A, Lenarz T, Staecker H. Evaluating Neurotrophin Signaling Using MicroRNA Perilymph Profiling in Cochlear Implant Patients With and Without Residual Hearing. (https://journals.lww.com/otology-neurotology/Abstract/9000/Evaluating_Neurotrophin_Signaling_Using_MicroRNA.95672.aspx) Otol Neurotol. 2021 May 10. doi: 10.1097/MAO.0000000000003182. Online ahead of print.

Harre J, Heinkele L, Steffens M, Warnecke A, Lenarz T, Just I, Rohrbeck A. Potentiation of Brain-Derived Neurotrophic Factor-Induced Protection of Spiral Ganglion Neurons by C3 Exoenzyme/Rho Inhibitor. (https://www.frontiersin.org/articles/10.3389/fncel.2021.602897/full) Front Cell Neurosci. 2021 Mar 11;15:602897. doi: 10.3389/fncel.2021.602897. eCollection 2021.

McLean WJ, Hinton AS, Herby JTJ, Salt AN, Hartsock JJ, Wilson S, Lucchino DL, Lenarz T, Warnecke A, Prenzler N, Schmitt H, King S, Jackson LE, Rosenbloom J, Atiee G, Bear M, Runge CL, Gifford RH, Rauch SD, Lee DJ, Langer R, Karp JM, Loose C, LeBel C. Improved speech intelligibility in subjects with stable sensorineural hearing loss following intratympanic dosing of FX-322 in a Phase 1b study. (https://journals.lww.com/otology-neurotology/Abstract/9000/Improved_Speech_Intelligibility_in_Subjects_With.95768.aspx) Otol Neurotol. 2021 Feb 22. doi: 10.1097/MAO.0000000000003120. Online ahead of print.

 

 

 

2020
Warnecke A, Harre J, Staecker H, Prenzler N, Strunk D, Couillard-Despres S, Romanelli P, Hollerweger J, Lassacher T, Auer D, Pachler K, Wietzorrek G, Köhl U, Lenarz T, Schallmoser K, Laner-Plamberger S, Falk CS, Rohde E, Gimona M. Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo.(https://onlinelibrary.wiley.com/doi/10.1002/ctm2.262) Clin Transl Med. 2020 Dec;10(8):e262. doi: 10.1002/ctm2.262.

Espersen J, Weber U, Römer-Franz A, Lenarz T, Stolle SRO, Warnecke A. Level of sex hormones and their association with acetylsalicylic acid intolerance and nasal polyposis. (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243732) PLoS One. 2020 Dec 17;15(12):e0243732. doi: 10.1371/journal.pone.0243732.

Schulze J, Staecker H, Wedekind D, Lenarz T, Warnecke A. Expression pattern of brain-derived neurotrophic factor and its associated receptors: Implications for exogenous neurotrophin application.(https://www.sciencedirect.com/science/article/pii/S0378595520303695?via%3Dihub) Hear Res 2020. doi:10.1016/j.heares.2020.108098

Salcher R, Boruchov A, Timm M, Steffens M, Giesemann A, Lenarz T, Warnecke A. On the Intracochlear Location of Straight Electrode Arrays After Cochlear Implantation: How Lateral Are Lateral Wall Electrodes? (https://journals.lww.com/otology-neurotology/Fulltext/2021/02000/On_the_Intracochlear_Location_of_Straight.8.aspx) Otol Neurotol. 2020 Sep 22. doi: 10.1097/MAO.0000000000002880

Knipper M, van Dijk P, Schulze H, Mazurek B, Krauss P, Scheper V, Warnecke A, Schlee W, Schwabe K, Singer W, Braun C, Delano PH, Fallgatter AJ, Ehlis AC, Searchfield GD, Munk MHJ, Baguley DM, Rüttiger L. The Neural Bases of Tinnitus: Lessons from Deafness and Cochlear Implants. (https://www.jneurosci.org/content/40/38/7190/tab-article-info) J Neurosci. 2020 Sep 16;40(38):7190-7202. doi: 10.1523/JNEUROSCI.1314-19.2020.

Shew M, Wichova H, Bur A, Koestler DC, St Peter M, Warnecke A, Staecker H. MicroRNA Profiling as a Methodology to Diagnose Ménière's Disease: Potential Application of Machine Learning. (https://journals.sagepub.com/doi/10.1177/0194599820940649) Otolaryngol Head Neck Surg. 2020 Jul 14:194599820940649. doi: 10.1177/0194599820940649.

Prenzler NK, Weller T, Steffens M, Lesinski-Schiedat A, Büchner A, Lenarz T, Warnecke A. Impedance Values Do Not Correlate With Speech Understanding in Cochlear Implant Recipients. (https://www.x-mol.com/paper/1294385303076347904) Otol Neurotol. 2020 Jul 14. doi: 10.1097/MAO.0000000000002743.

Heilen S, Lang CP, Warnecke A, Lenarz T, Durisin M. Exploratory tympanotomy in sudden sensorineural hearing loss for the identification of a perilymphatic fistula - retrospective analysis and review of the literature. (https://www.cambridge.org/core/journals/journal-of-laryngology-and-otology/article/exploratory-tympanotomy-in-sudden-sensorineural-hearing-loss-for-the-identification-of-a-perilymphatic-fistula-retrospective-analysis-and-review-of-the-literature/9BD2C2A02F50183A6C52DDB8DF41DFE8) J Laryngol Otol. 2020 Jun;134(6):501-508. doi: 10.1017/S0022215120000948.

Peter MN, Paasche G, Reich U , Lenarz T , Warnecke A. Differential Effects of Low- And High-Dose Dexamethasone on Electrically Induced Damage of the Cultured Organ of Corti. (https://link.springer.com/article/10.1007%2Fs12640-020-00228-7)** Neurotox. 03 June 2020. doi: 10.1007/s12640-020-00228-7.

Prenzler NK, Salcher R, Lenarz T, Gaertner L, Warnecke A. Dose-Dependent Transient Decrease of Impedances by Deep Intracochlear Injection of Triamcinolone With a Cochlear Catheter Prior to Cochlear Implantation-1 Year Data. (https://doi.org/10.3389/fneur.2020.00258) Front Neurol. 2020 Apr 15;11:258. doi:10.3389/fneur.2020.00258. eCollection 2020.

El-Saied S, Schmitt H, Durisin M, Joshua BZ, Abu Tailakh M, Prenzler N, Lenarz T, Kaplan DM, Lewis EC, Warnecke A. Endogenous α1-antitrypsin levels in the perilymphatic fluid correlates with severity of hearing loss.(https://doi.org/10.1111/coa.13541) Clin Otolaryngol. 2020 Apr 4. doi: 10.1111/coa.13541.

Majdani E, Majdani O, Steffens M, Warnecke A, Lesinski-Schiedat A, Lenarz T, Götz F. Dimensions of artefacts caused by cochlear and auditory brainstem implants in magnetic resonance imaging.(https://doi.org/10.1080/14670100.2019.1668617) Cochlear Implants Int. 2020 Mar;21(2):67-74. doi: 10.1080/14670100.2019.1668617.

Zelener F, Majdani O, Roemer A, Lexow GJ, Giesemann A, Lenarz T, Warnecke A. Relations Between Scalar Shift and Insertion Depth in Human Cochlear Implantation. (https://journals.lww.com/otology-neurotology/FullText/2020/02000/Relations_Between_Scalar_Shift_and_Insertion_Depth.10.aspx) Otol Neurotol. 2020 Feb;41(2):178-185. doi: 10.1097/MAO.0000000000002460.

Claußen M, Schulze J, Nothwang HG. Loss of inner hair cell ribbon synapses and auditory nerve fiber regression in Cldn14 knockout mice. (https://doi.org/10.1016/j.heares.2020.107950) Hear Res 2020;391:107950. doi: 10.1016/j.heares.2020.107950.

2019
Weininger O, Warnecke A, Lesinski-Schiedat A, Lenarz T, Stolle S. Computational analysis based on audioprofiles: A new possibility for patient stratification in office-based otology. (https://doi.org/10.4081/audiores.2019.230) Audiol Res. 2019 Nov 5;9(2):230. doi: 10.4081/audiores.2019.230. eCollection 2019 Sep 2.

Wang H, Stahl F, Scheper T, Steffens M, Warnecke A, Zeilinger C. Microarray-Based Screening System Identifies Temperature-Controlled Activity of Connexin 26 That Is Distorted by Mutations. (https://www.nature.com/articles/s41598-019-49423-3) Scientific Reports 9, no. 1 (December 19, 2019): 13543. doi:10.1038/s41598-019-49423-3.

Schulze J, Nolte L, Lyutenski S, Tinne N, Heinemann D, Ripken T, Willaredt MA, Nothwang HG, Lenarz T, Warnecke A. Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes. (https://doi.org/10.1007/s00106-019-0654-2) HNO. 2019 Aug;67(8):590-599. doi: 10.1007/s00106-019-0652-4.

Schulze J, Nolte L, Lyutenski S, Tinne N, Heinemann D, Ripken T, Willaredt MA, Nothwang HG, Lenarz T, Warnecke A. Scannende laseroptische Tomographie in einem neuropathischen Mausmodell. (https://doi.org/10.1007/s00106-019-0652-4)** HNO. 2019 Aug;67(8):590-599. doi: 10.1007/s00106-019-0652-4.

Warnecke A, Prenzler NK, Schmitt H, Daemen K, Keil J, Dursin M, Lenarz T, Falk CS. Defining the Inflammatory Microenvironment in the Human Cochlea by Perilymph Analysis: Toward Liquid Biopsy of the Cochlea. (https://doi.org/10.3389/fneur.2019.00665) Front Neurol. 2019 Jun 25;10:665. doi: 10.3389/fneur.2019.00665.

Schilder AGM, Su MP, Blackshaw H, Lustig L, Staecker H, Lenarz T, Safieddine S, Gomes-Santos CS, Holme R, Warnecke A. Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders. (https://europepmc.org/article/med/31083073) Otol Neurotol. 2019 Jun;40(5):559-570. doi: 10.1097/MAO.0000000000002194.

de Vries I, Schmitt H, Lenarz T, Prenzler N, Alvi S, Staecker H, Durisin M, Warnecke A. Detection of BDNF-Related Proteins in Human Perilymph in Patients With Hearing Loss. (https://doi.org/10.3389/fnins.2019.00214) Front Neurosci. 2019 Mar 26;13:214. doi: 10.3389/fnins.2019.00214.

Peter MN, Paasche G, Reich U, Lenarz T, Warnecke A. Reactions in the organ of Corti to electrical stimulation : StED technology for detecting changes. (https://link.springer.com/article/10.1007%2Fs00106-019-0641-7) HNO. 2019 Apr;67(4):251-257. doi: 10.1007/s00106-019-0641-7. German.

Peter MN, Warnecke A, Reich U, Olze H, Szczepek AJ, Lenarz T, Paasche G. Influence of In Vitro Electrical Stimulation on Survival of Spiral Ganglion Neurons. (https://link.springer.com/article/10.1007/s12640-019-00017-x) Neurotox Res. 2019 Jul;36(1):204-216. doi: 10.1007/s12640-019-00017-x.

2018
Schulze J, Sasse S, Prenzler N, Staecker H, Mellott AJ, Roemer A, Durisin M, Lenarz T, Warnecke A. Microenvironmental support for cell delivery to the inner ear. (https://doi.org/10.1016/j.heares.2018.06.015) Hear Res. 2018 Oct;368:109-122. doi: 10.1016/j.heares.2018.06.015.

Shew M, Warnecke A, Lenarz T, Schmitt H, Gunewardena S, Staecker H. Feasibility of microRNA profiling in human inner ear perilymph. (https://journals.lww.com/neuroreport/Fulltext/2018/08010/Feasibility_of_microRNA_profiling_in_human_inner.4.aspx) Neuroreport. 2018 Aug 1;29(11):894-901. doi: 10.1097/WNR.0000000000001049.

Schilder AGM, Blackshaw H, Lenarz T, Warnecke A, Lustig LR, Staecker H. Biological Therapies of the Inner Ear: What Otologists Need to Consider. Otol Neurotol. (https://insights.ovid.com/crossref?an=00129492-201802000-00001) 2018 Feb;39(2):135-137. doi: 10.1097/MAO.0000000000001689.

Prenzler NK, Salcher R, Timm M, Gaertner L, Lenarz T, Warnecke A. Intracochlear administration of steroids with a catheter during human cochlear implantation: a safety and feasibility study. (https://link.springer.com/article/10.1007%2Fs13346-018-0539-z) Drug Deliv Transl Res. 2018 May 14. doi: 10.1007/s13346-018-0539-z.

Yue Q, Stahl F, Plettenburg O, Kirschning A, Warnecke A, Zeilinger C. Non-competitive effect of gambogic acid displaces fluorescence labelled ATP but requires ATP for binding to Hsp90/HtpG. (https://doi.org/10.1021/acs.biochem.8b00155) Biochemistry. 2018 Apr 17. doi:10.1021/acs.biochem.8b00155.

Schmidt N, Schulze J, Warwas DP, Ehlert N, Lenarz T, Warnecke A, Behrens P. Long-term delivery of brain-derived neurotrophic factor (BDNF) from nanoporous silica nanoparticles improves the survival of spiral ganglion neurons in vitro. (https://doi.org/10.1371/journal.pone.0194778) PLoS One. 2018 Mar 27;13(3). doi: e0194778.

Schmitt H, Roemer A, Zeilinger C, Salcher R, Durisin M, Staecker H, Lenarz T, Warnecke A. Heat Shock Proteins in Human Perilymph: Implications for Cochlear Implantation. (https://insights.ovid.com/crossref?an=00129492-201801000-00007) Otol Neurotol. 2018 Jan;39(1):37-44.

Stolle M, Schulze J, Roemer A, Lenarz T, Durisin M, Warnecke A. Human Plasma Rich in Growth Factors Improves Survival and Neurite Outgrowth of Spiral Ganglion Neurons In Vitro. (https://www.liebertpub.com/doi/10.1089/ten.TEA.2017.0120?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&) Eng Part A. 2018 Mar;24(5-6):493-501.doi: 10.1089/ten.TEA.2017.0120.

2017
Roemer A, Warnecke A, Lenarz T, Stolle SRO. Successful Treatment of Intractable Facial Osteomyelitis with Autologous PRP and Gentamicin. (https://www.semanticscholar.org/paper/Successful-Treatment-of-Intractable-Facial-with-PRP-Roemer-Warnecke/62a50b9bacd6128d499a92bd8a7bb1da25759ca5) Clin Otorlyryngol (2017)1:1 011.

Höhl M, DeTemple D, Lyutenski S, Leuteritz G, Varkentin A, Schmitt HA, Lenarz T, Roth B, Meinhardt-Wollweber M, Morgner U. Optical properties of the human round window membrane. (https://doi.org/10.1117/1.JBO.22.10.105007) J Biomed Opt. 2017 Oct;22(10):1-7. doi: 10.1117/1.JBO.22.10.105007.

Schulze J, Kaiser O, Paasche G, Lamm H, Pich A, Hoffmann A, Lenarz T, Warnecke A.Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics.(https://doi.org/10.1371/journal.pone.0178182) PLoS One. 2017 May 23;12(5).doi: e0178182.

Trebesch S, Koch T, Warnecke A, Lenarz T, Stolle S. Objective and subjective assessment of outcomes after sinus surgery in sixty patients.(https://doi.org/10.1111/coa.12897) Clin Otolaryngol. 2017 May 02;42(6):1400-1403. doi: 10.1111/coa.12897.

Schmitt HA, Pich A, Schröder A, Scheper V, Lilli G, Reuter G, Lenarz T. Proteome Analysis of Human Perilymph Using an Intraoperative Sampling Method. (https://pubs.acs.org/doi/10.1021/acs.jproteome.6b00986) J Proteome Res. 2017 May 5;16(5):1911-1923. doi: 10.1021/acs.jproteome.6b00986. Epub 2017 Apr 13.

Nolte L, Tinne N, Schulze J, Heinemann D, Antonopoulos GC, Meyer H, Nothwang HG, Lenarz T, Heisterkamp A, Warnecke A, Ripken T. Scanning laser optical tomography for in toto imaging of the murine cochlea. (https://doi.org/10.1371/journal.pone.0175431) PLOS One. 2017Apr 7. doi: e0175431.

Roemer A, Staecker H, Sasse S, Lenarz T, Warnecke A. Biologische Therapien in der Otologie. (https://link.springer.com/article/10.1007%2Fs00106-016-0304-x) HNO. 2017 Feb 15. doi: 10.1007/s00106-016-0304-x.

Vor 2016
Roger Y, Schäck LM, Koroleva A, Noack S, Kurselis K, Krettek C, Chichkov B, Lenarz T, Warnecke A, Hoffmann A. Grid-like surface structures in thermoplastic polyurethane induce anti-inflammatory and anti-fibrotic processes in bone marrow-derived mesenchymal stem cells. (http://www.sciencedirect.com/science/article/pii/S0927776516304507) Colloids Surf B Biointerfaces. 2016 Dec;148:104-115. doi: 10.1016/j.colsurfb.2016.06.024. Epub 2016 Jun 16.

Roemer A, Köhl U, Majdani O, Klöß S, Falk C, Haumann S, Lenarz T, Kral A, Warnecke A. Biohybrid cochlear implants in human neurosensory restoration. (http://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0408-y) Stem Cell Res Ther. 2016 Oct 7;7(1):148. doi: 10.1186/s13287-016-0408-y

Schäck L, Budde S, Lenarz T, Krettek C, Gross G, Windhagen H, Hoffmann A, Warnecke A. Induction of neuronal-like phenotype in human mesenchymal stem cells by overexpression of Neurogenin1 and treatment with neurotrophins. (http://www.sciencedirect.com/science/article/pii/S0040816616300805) Tissue Cell. 2016 Oct;48(5):524-32. doi: 10.1016/j.tice.2016.06.011. Epub 2016 Jun 27.

Hadler C, Aliuos P, Brandes G, Warnecke A, Bohlmann J, Dempwolf W, Menzel H, Lenarz T, Reuter G, Wissel K2. Polymer Coatings of Cochlear Implant Electrode Surface - An Option for Improving Electrode-Nerve-Interface by Blocking Fibroblast Overgrowth. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157710) PLoS One. 2016 Jul;11(7):e0157710. doi: 10.1371/journal.pone.0157710. eCollection 2016.

Burblies N, Schulze J, Schwarz HC, Kranz K, Motz D, Vogt C, Lenarz T, Warnecke A, Behrens P. Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158571) PLoS One. 2016 Jul;11(7):e0158571. doi: 10.1371/journal.pone.0158571. eCollection 2016.

Lamm H, Müller-Kortkamp C, Warnecke A, Pohl F, Paasche G, Lenarz T, Stolle SR. Concurrent hyperbaric oxygen therapy and intratympanic steroid application as salvage therapy after severe sudden sensorineural hearing loss. (http://onlinelibrary.wiley.com/doi/10.1002/ccr3.510/abstract;jsessionid=ACCD40899FAD7B88D1475519CDC70038.f02t03)** Clin Case Rep. 2016 Feb;4(3):287-93. doi: 10.1002/ccr3.510. eCollection 2016.

Aliuos P, Schulze J, Schomaker M, Reuter G, Stolle SR, Werner D, Ripken T, Lenarz T, Warnecke A. Magnetic Beads Enhance Adhesion of NIH 3T3 Fibroblasts: A Proof-of-Principle In Vitro Study for Implant-Mediated Long-Term Drug Delivery to the Inner Ear. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150057) PLoS One. 2016 Feb;11(2):e0150057. doi: 10.1371/journal.pone.0150057. eCollection 2016.

Burke WF, Warnecke A, Schöner-Heinisch A, Lesinski-Schiedat A, Maier H, Lenarz T. Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients. (http://www.sciencedirect.com/science/article/pii/S0378595516000034) Hear Res. 2016 Mar;333:77-86. doi: 10.1016/j.heares.2016.01.006. Epub 2016 Jan 15.

Schwieger J, Warnecke A, Lenarz T, Esser KH, Scheper V. Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532470/) PLoS One. 2015 Aug 11;10(8):e0133680. doi: 10.1371/journal.pone.0133680. eCollection 2015.

Helmstaedter V, Tellkamp R, Majdani O, Warnecke A, Lenarz T, Durisin M. High-frequency jet ventilation for endolaryngotracheal surgery - chart review and procedure analysis from the surgeon's and the anaesthesiologist's point of view. (http://onlinelibrary.wiley.com/doi/10.1111/coa.12376/full) Clin Otolaryngol. 2015 Aug;40(4):341-8. doi: 10.1111/coa.12376.

Reich U, Warnecke A, Szczepek AJ, Mazurek B, Olze H. Establishment of an experimental system to study the influence of electrical field on cochlear structures. (http://www.sciencedirect.com/science/article/pii/S0304394015003845) Neurosci Lett. 2015 Jul 10;599:38-42. doi: 10.1016/j.neulet.2015.05.027. Epub 2015 May 19.

Durisin M, Büchner A, Lesinski-Schiedat A, Bartling S, Warnecke A, Lenarz T. Cochlear implantation in children with bacterial meningitic deafness: The influence of the degree of ossification and obliteration on impedance and charge of the implant. (http://www.maneyonline.com/doi/full/10.1179/1754762814Y.0000000094) Cochlear Implants Int. 2015 May;16(3):147-58. doi: 10.1179/1754762814Y.0000000094. Epub 2014 Aug 17.

Wenzel GI, Sarnes P, Warnecke A, Stöver T, Jäger B, Lesinski-Schiedat A, Lenarz T. Non-penetrating round window electrode stimulation for tinnitus therapy followed by cochlear implantation. (http://link.springer.com/article/10.1007/s00405-014-3413-8/fulltext.html) Eur Arch Otorhinolaryngol. 2014 Dec 6. doi: 10.1007/s00405-014-3413-8 [Epub ahead of print]

Wrzeszcz A, Steffens M, Balster S, Warnecke A, Dittrich B, Lenarz T, Reuter G. Hydrogel coated and dexamethasone releasing cochlear implants: Quantification of fibrosis in guinea pigs and evaluation of insertion forces in a human cochlea model. (http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33187/abstract) J Biomed Mater Res B Appl Biomater. 2014 May 8. doi: 10.1002/jbm.b.33187. [Epub ahead of print]

Kranz K, Warnecke A, Durisin M, Lenarz T, Scheper V. Phosphodiesterase type 4 inhibitor Rolipram improves survival of spiral ganglion neurons in vitro. (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0092157) Accepted February 2014 in PLOSone

Kaiser O, Alious P, Wissel K, Lenarz T, Werner D, Reuter G, Kral A, Warnecke A. Dissociated neurons and glial cells derived from rat inferior colliculi after digestion with papain. (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0080490) PLoS One. 2013 Dec 12;8(12):e80490.

Balster S, Wenzel GI, Warnecke A, Steffens M, Rettenmaier A, Zhang K, Lenarz T, Reuter G. Optical cochlear implant: evaluation of insertion forces of optical fibres in a cochlear model and of traumata in human temporal bones. (http://www.degruyter.com/view/j/bmte.2014.59.issue-1/bmt-2013-0038/bmt-2013-0038.xml;jsessionid=B859C5C9F2215DF8FB96F3A590E9A25E) Biomed Tech (Berl). 2014 Feb 1;59(1):19-28.

Kaiser O, Paasche G, Stöver T, Ernst S, Lenarz T, Kral A, Warnecke A. TGF-beta superfamily member activin A acts with BDNF and erythropoietin to improve survival of spiral ganglion neurons in vitro.](http://www.sciencedirect.com/science/article/pii/S0028390813003651) Neuropharmacology. 2013 Aug 22;75C:416-425. doi: 10.1016/j.neuropharm.2013.08.008.

Aliuos P, Sen A, Reich U, Dempwolf W, Warnecke A, Hadler C, Lenarz T, Menzel H, Reuter G. Inhibition of fibroblast adhesion by covalently immobilized protein repellent polymer coatings studied by single cell force spectroscopy. (http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.34686/abstract) J Biomed Mater Res A. 2013 Apr 18. doi: 10.1002/jbm.a.34686.

Alious P, Fadeeva E, Badar M, Winkel A, Mueller PP, Warnecke A, Chichkov B, Lenarz T, Reich U, Reuter G. Evaluation of single-cell force spectroscopy and microscopy to determine cell interactions with femtosecond-laser microstructured titanium surfaces. (http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.34401/abstract) J Biomed Res Part A 2013;101(4):981-990.

Warnecke A, Sasse S, Wenzel GI, Hoffmann A, Gross G, Paasche G, Scheper V, Reich U, Esser K-H, Lenarz T, Stöver T, Wissel K. Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo. (http://www.sciencedirect.com/science/article/pii/S0378595512000937). Hear Res. 2012 Jul;289(1-2):86-97.

Reich U, Fadeeva E, Warnecke A, Paasche G, Mueller P, Chichkov B, Stöver T, Lenarz T, Reuter G. Directing neuronal cell growth on implant material surfaces by microstructuring. (http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.32656/abstract) Journal of Biomedical Materials Research: Part B - Applied Biomaterials. 2012 May;100(4):940-947.

Warnecke A, Scheper V, Buhr I, Wenzel GI, Wissel K, Paasche G, Berkingali N, Jørgensen JR, Lenarz T, Stöver T. Artemin improves survival of spiral ganglion neurons in vivo and in vitro. (http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.32656/abstract) Neuroreport. 2010 May 12;21(7):517-21.

Wenzel G, Warnecke A, Stöver T, Lenarz T. Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case series. (http://link.springer.com/article/10.1007%2Fs00405-009-1126-1) Eur Arch Otorhinolaryngol. 2010 May;267(5):691-699.

Kramer F, Stöver T, Warnecke A, Diensthuber M, Lenarz T, Wissel K. BDNF mRNA expression is significantly upregulated in vestibular schwannomas and correlates with proliferative activity. (http://link.springer.com/article/10.1007%2Fs11060-009-0063-6) J Neurooncol. 2010 May;98(1):31-39.

Warnecke A, Averbeck T, Soudah B, Wenzel GI, Lenarz T, Stöver T. Contact endoscopy for the evaluation of the pharyngeal and laryngeal mucosa. (http://onlinelibrary.wiley.com/doi/10.1002/lary.20732/abstract) Laryngoscope. 2010 Feb;120(2):253-258.

Scheper V, Paasche G, Miller JM, Warnecke A, Berkingali N, Lenarz T, Stöver T. Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs. (http://onlinelibrary.wiley.com/doi/10.1002/jnr.21964/abstract) J Neurosci Res. 2009 May 1;87(6):1389-1399.

Warnecke A, Luessen P, Sandmann J, Ikic M, Rossa S, Gutzki FM, Stichtenoth DO, Tsikas D. Application of a stable-isotope dilution technique to study the pharmacokinetics of human (15)N-labelled S-nitrosoalbumin in the rat: Possible mechanistic and biological implications. (http://www.sciencedirect.com/science/article/pii/S1570023208008702) J Chromatogr B Analyt Technol Biomed Life Sci. 2009 May;877(13):1375-1387.

Berkingali N, Warnecke A, Gomes P, Paasche G, Tack J, Lenarz T, Stöver T. Neurite outgrowth on cultured spiral ganglion neurons induced by erythropoietin. (http://www.sciencedirect.com/science/article/pii/S0378595508001317) Hear Res. 2008 Sep;243(1-2):121-126.

Wissel K, Stöver T, Hofmann N-S, Chernajovsky Y, Daly G, Sasse S, Warnecke A, Lenarz T, Gross G, Hoffmann A. Fibroblast-mediated GDNF-delivery induces neuronal-like outgrowth in PC12 cells. (http://journals.lww.com/otology-neurotology/pages/articleviewer.aspx?year=2008&issue=06000&article=00011&type=abstract) Otol Neurotol. 2008 Jun;29(4):475-481.

Torkos A, Wissel K, Warnecke A, Lenarz T, Stöver T. Technical report: Laser microdissection and pressure catapulting is superior to conventional manual dissection for isolating pure spiral ganglion fractions from the cochlea. (http://www.sciencedirect.com/science/article/pii/S0378595507002365) Hear Res. 2008 Jan;235(1-2):8-14.

Warnecke A, Wissel K, Hoffmann A, Hofmann N-S, Berkingali N, Groß G, Lenarz T, Stöver T. The biological effects of cell-delivered BDNF on cultured spiral ganglion cells Neuroreport. (http://journals.lww.com/neuroreport/pages/articleviewer.aspx?year=2007&issue=10290&article=00010&type=abstract) 2007 Oct;18(16)1683-1686.

Lesinski-Schiedat A, Illg A, Warnecke A, Heerman R, Bertram B, Lenarz T. Kochleaimplantation bei Kindern im 1. Lebensjahr. Vorläufige Ergebnisse. (http://www.springermedizin.de/kochleaimplantation-bei-kindern-im-1lebensjahr/79456.html) HNO. 2005 Jul;54(7):565-572.

Warnecke A, Averbeck T, Wurster U, Harmening M, Lenarz T, Stöver T. Diagnostic Relevance of β2-Transferrin for the Detection of Cerebrospinal Fluid Fistulas. (http://archotol.jamanetwork.com/article.aspx?articleid=648189) Arch Otolaryngol, Head Neck Surg. 2004 Oct;130(10):1178-1184.

Savva A, Taylor M, Beatty CW. Management of Cerebrospinal Fluid Leaks Involving the Temporal Bone: Report on 92 Patients. (http://onlinelibrary.wiley.com/doi/10.1097/00005537-200301000-00010/abstract) Laryngoscope 2003 Jan;113(1):50-56.

Strome SE, Savva A, Brisset AE, Gostout BS, Lewis J, Clayton AC, McGovern R, Weaver AE, Persing D, Kasperbauer JL. Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations. (http://clincancerres.aacrjournals.org/content/8/4/1093.long) Clin Cancer Res. 2002 Apr;8(4):1093-1100.

Khabie N, Savva A, Kasperbauer JL, McGovern R, Gostout B, Strome SE. Epstein-Barr Virus DNA is not increased in Tonsillar Carcinoma. (http://onlinelibrary.wiley.com/enhanced/doi/10.1097/00005537-200105000-00011/) Laryngoscope. 2001 May;111(5):811-814.

Tsikas D, Sandmann J, Lueßen P, Savva A, Rossa S, Stichtenoth DO, Frölich JC. S-Transnitrosylation of albumin in human plasma and blood in vitro and in vivo in the rat. (http://www.sciencedirect.com/science/article/pii/S0167483801001662) Biochem Biophys. 2001 Apr;1546(2):422-434.

Tsikas D, Sandmann J, Savva A, Lueßen P, Böger RH, Gutzki F-M, Mayer B, Frölich JC. Assessment of nitric oxide synthase activity in vitro and in vivo by gas chromatography-mass spectrometry. (http://www.sciencedirect.com/science/article/pii/S0378434700001420) J Chrom B. 2000 May;742(1):143-153.

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Schlagwörter
Cochlea, Cochlea Implantat (CI), Extrazelluläre Vesikel (EVs), Spiralganglienneurone (SGN), Mesenchymale Stromazellen (MSC), Perilymphe, Brain-derived neurotrophic factor (BDNF)
Kontakt

Prof. Dr. Athanasia Warnecke

+49 (0)511-532-1474

Warnecke.athanasia(at)mh-hannover.de

NIFE
Stadtfelddamm 34
30625 Hannover

Specials

Preise

2014 GEERS Preis

2009 Award of Excellence Academy Medical Techniques of the German Research Foundation

 

 

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