@phdthesis{Endlich2021,
  author    = {Endlich, Alexander Dominic},
  title     = {Die Rolle der Dsg3-Depletion in der Pathogenese des Pemphigus vulgaris},
  doi       = {10.25972/OPUS-22557},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225573},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Pemphigus vulgaris (PV) ist eine blasenbildende Autoimmunerkrankung, die durch Autoantik{\"o}rper gegen Dsg1 und Dsg3 gekennzeichnet ist. Der genaue Pathomechanismus, der zu einem PV-IgG vermittelten Verlust der interzellul{\"a}ren Adh{\"a}sion f{\"u}hrt, ist noch unklar. Die Dsg3-Depletion und die Modulation von Signalkaskaden stellen hierbei kennzeichnende Merkmale der Erkrankung dar. Mit den Ergebnissen der vorliegenden Arbeit ist eine bessere Einordnung der Dsg3-Depletion in den pathogenetischen Kontext von Pemphigus vulgaris m{\"o}glich. Die Experimente zeigen, dass die Dsg3-Depletion von Differenzierungsprozessen abh{\"a}ngig ist und mit einem Adh{\"a}sionsverlust einhergehen kann. Die Hemmung der PKC verhindert hierbei sowohl die PV-IgG vermittelten Effekte in der Zellkultur als auch die Blasenbildung im Mausmodell in vivo und in humaner Haut ex vivo. Des Weiteren liefert die Arbeit neue Erkenntnisse, welche f{\"u}r die suprabasale Lokalisation der Blasenbildung bedeutsam sein k{\"o}nnten.},
  subject      = {Zelladh{\"a}sion},
  language  = {de}
}
@article{RajendranBoettigerDentzienetal.2021,
  author    = {Rajendran, Ranjithkumar and B{\"o}ttiger, Gregor and Dentzien, Niklas and Rajendran, Vinothkumar and Sharifi, Bischand and Erg{\"u}n, S{\"u}leyman and Stadelmann, Christine and Karnati, Srikanth and Berghoff, Martin},
  title     = {Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {6},
  issn      = {2073-4409},
  doi       = {10.3390/cells10061318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239600},
  year      = {2021},
  abstract  = {Fibroblast growth factor (FGF) signaling is involved in the pathogenesis of multiple sclerosis (MS). Data from neuropathology studies suggest that FGF signaling contributes to the failure of remyelination in MS. In MOG\(_{35-55}\)-induced EAE, oligodendrocyte-specific deletion of FGFR1 and FGFR2 resulted in a less severe disease course, reduced inflammation, myelin and axon degeneration and changed FGF/FGFR and BDNF/TrkB signaling. Since signaling cascades in oligodendrocytes could not be investigated in the EAE studies, we here aimed to characterize FGFR-dependent oligodendrocyte-specific signaling in vitro. FGFR inhibition was achieved by application of the multi-kinase-inhibitor dovitinib and the FGFR1/2/3-inhibitor AZD4547. Both substances are potent inhibitors of FGF signaling; they are effective in experimental tumor models and patients with malignancies. Effects of FGFR inhibition in oligodendrocytes were studied by immunofluorescence microscopy, protein and gene analyses. Application of the tyrosine kinase inhibitors reduced FGFR1, phosphorylated ERK and Akt expression, and it enhanced BDNF and TrkB expression. Furthermore, the myelin proteins CNPase and PLP were upregulated by FGFR inhibition. In summary, inhibition of FGFR signaling in oligodendrocytes can be achieved by application of tyrosine kinase inhibitors. Decreased phosphorylation of ERK and Akt is associated with an upregulation of BDNF/TrkB signaling, which may be responsible for the increased production of myelin proteins. Furthermore, these data suggest that application of FGFR inhibitors may have the potential to promote remyelination in the CNS.},
  language  = {en}
}
@article{HorderGuazaLasherasGrummeletal.2021,
  author    = {Horder, Hannes and Guaza Lasheras, Mar and Grummel, Nadine and Nadernezhad, Ali and Herbig, Johannes and Erg{\"u}n, S{\"u}leyman and Teßmar, J{\"o}rg and Groll, J{\"u}rgen and Fabry, Ben and Bauer-Kreisel, Petra and Blunk, Torsten},
  title     = {Bioprinting and differentiation of adipose-derived stromal cell spheroids for a 3D breast cancer-adipose tissue model},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {4},
  doi       = {10.3390/cells10040803},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236496},
  year      = {2021},
  abstract  = {Biofabrication, including printing technologies, has emerged as a powerful approach to the design of disease models, such as in cancer research. In breast cancer, adipose tissue has been acknowledged as an important part of the tumor microenvironment favoring tumor progression. Therefore, in this study, a 3D-printed breast cancer model for facilitating investigations into cancer cell-adipocyte interaction was developed. First, we focused on the printability of human adipose-derived stromal cell (ASC) spheroids in an extrusion-based bioprinting setup and the adipogenic differentiation within printed spheroids into adipose microtissues. The printing process was optimized in terms of spheroid viability and homogeneous spheroid distribution in a hyaluronic acid-based bioink. Adipogenic differentiation after printing was demonstrated by lipid accumulation, expression of adipogenic marker genes, and an adipogenic ECM profile. Subsequently, a breast cancer cell (MDA-MB-231) compartment was printed onto the adipose tissue constructs. After nine days of co-culture, we observed a cancer cell-induced reduction of the lipid content and a remodeling of the ECM within the adipose tissues, with increased fibronectin, collagen I and collagen VI expression. Together, our data demonstrate that 3D-printed breast cancer-adipose tissue models can recapitulate important aspects of the complex cell-cell and cell-matrix interplay within the tumor-stroma microenvironment},
  language  = {en}
}
@article{JordanJaeckleScheidtetal.2021,
  author    = {Jordan, Martin C. and J{\"a}ckle, Veronika and Scheidt, Sebastian and Gilbert, Fabian and H{\"o}lscher-Doht, Stefanie and Erg{\"u}n, S{\"u}leyman and Meffert, Rainer H. and Heintel, Timo M.},
  title     = {Trans-obturator cable fixation of open book pelvic injuries},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-92755-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261212},
  year      = {2021},
  abstract  = {Operative treatment of ruptured pubic symphysis by plating is often accompanied by complications. Trans-obturator cable fixation might be a more reliable technique; however, have not yet been tested for stabilization of ruptured pubic symphysis. This study compares symphyseal trans-obturator cable fixation versus plating through biomechanical testing and evaluates safety in a cadaver experiment. APC type II injuries were generated in synthetic pelvic models and subsequently separated into three different groups. The anterior pelvic ring was fixed using a four-hole steel plate in Group A, a stainless steel cable in Group B, and a titan band in Group C. Biomechanical testing was conducted by a single-leg-stance model using a material testing machine under physiological load levels. A cadaver study was carried out to analyze the trans-obturator surgical approach. Peak-to-peak displacement, total displacement, plastic deformation and stiffness revealed a tendency for higher stability for trans-obturator cable/band fixation but no statistical difference to plating was detected. The cadaver study revealed a safe zone for cable passage with sufficient distance to the obturator canal. Trans-obturator cable fixation has the potential to become an alternative for symphyseal fixation with less complications.},
  language  = {en}
}
@phdthesis{Andreska2021,
  author    = {Andreska, Thomas},
  title     = {Effects of dopamine on BDNF / TrkB mediated signaling and plasticity on cortico-striatal synapses},
  doi       = {10.25972/OPUS-17431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174317},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Progressive loss of voluntary movement control is the central symptom of Parkinson's disease (PD). Even today, we are not yet able to cure PD. This is mainly due to a lack of understanding the mechanisms of movement control, network activity and plasticity in motor circuits, in particular between the cerebral cortex and the striatum. Brain-derived neurotrophic factor (BDNF) has emerged as one of the most important factors for the development and survival of neurons, as well as for synaptic plasticity. It is thus an important target for the development of new therapeutic strategies against neurodegenerative diseases. Together with its receptor, the Tropomyosin receptor kinase B (TrkB), it is critically involved in development and function of the striatum. Nevertheless, little is known about the localization of BDNF within presynaptic terminals in the striatum, as well as the types of neurons that produce BDNF in the cerebral cortex. Furthermore, the influence of midbrain derived dopamine on the control of BDNF / TrkB interaction in striatal medium spiny neurons (MSNs) remains elusive so far. Dopamine, however, appears to play an important role, as its absence leads to drastic changes in striatal synaptic plasticity. This suggests that dopamine could regulate synaptic activity in the striatum via modulation of BDNF / TrkB function. To answer these questions, we have developed a sensitive and reliable protocol for the immunohistochemical detection of endogenous BDNF. We find that the majority of striatal BDNF is provided by glutamatergic, cortex derived afferents and not dopaminergic inputs from the midbrain. In fact, we found BDNF in cell bodies of neurons in layers II-III and V of the primary and secondary motor cortex as well as layer V of the somatosensory cortex. These are the brain areas that send dense projections to the dorsolateral striatum for control of voluntary movement. Furthermore, we could show that these projection neurons significantly downregulate the expression of BDNF during the juvenile development of mice between 3 and 12 weeks. In parallel, we found a modulatory effect of dopamine on the translocation of TrkB to the cell surface in postsynaptic striatal Medium Spiny Neurons (MSNs). In MSNs of the direct pathway (dMSNs), which express dopamine receptor 1 (DRD1), we observed the formation of TrkB aggregates in the 6-hydroxydopamine (6-OHDA) model of PD. This suggests that DRD1 activity controls TrkB surface expression in these neurons. In contrast, we found that DRD2 activation has opposite effects in MSNs of the indirect pathway (iMSNs). Activation of DRD2 promotes a rapid decrease in TrkB surface expression which was reversible and depended on cAMP. In parallel, stimulation of DRD2 led to induction of phospho-TrkB (pTrkB). This effect was significantly slower than the effect on TrkB surface expression and indicates that TrkB is transactivated by DRD2. Together, our data provide evidence that dopamine triggers dual modes of plasticity on striatal MSNs by acting on TrkB surface expression in DRD1 and DRD2 expressing MSNs. This surface expression of the receptor is crucial for the binding of BDNF, which is released from corticostriatal afferents. This leads to the induction of TrkB-mediated downstream signal transduction cascades and long-term potentiation (LTP). Therefore, the dopamine-mediated translocation of TrkB could be a mediator that modulates the balance between dopaminergic and glutamatergic signaling to allow synaptic plasticity in a spatiotemporal manner. This information and the fact that TrkB is segregated to persistent aggregates in PD could help to improve our understanding of voluntary movement control and to develop new therapeutic strategies beyond those focusing on dopaminergic supply.},
  subject      = {Brain-derived neurotrophic factor},
  language  = {en}
}
@article{KarnatiSeimetzKleefeldtetal.2021,
  author    = {Karnati, Srikanth and Seimetz, Michael and Kleefeldt, Florian and Sonawane, Avinash and Madhusudhan, Thati and Bachhuka, Akash and Kosanovic, Djuro and Weissmann, Norbert and Kr{\"u}ger, Karsten and Erg{\"u}n, S{\"u}leyman},
  title     = {Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {8},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2021.649512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235631},
  year      = {2021},
  abstract  = {Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells via aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.},
  language  = {en}
}
@article{DoganScheuringWagneretal.2021,
  author    = {Dogan, Leyla and Scheuring, Ruben and Wagner, Nicole and Ueda, Yuichiro and Schmidt, Sven and W{\"o}rsd{\"o}rfer, Philipp and Groll, J{\"u}rgen and Erg{\"u}n, S{\"u}leyman},
  title     = {Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels},
  series = {Biofabrication},
  volume    = {13},
  journal   = {Biofabrication},
  number    = {4},
  doi       = {10.1088/1758-5090/ac26ac},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254046},
  year      = {2021},
  abstract  = {Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type I bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimics the embryonic steps of vessel formation during vasculogenesis. Histological evaluations at different time points of extrusion revealed the initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, endothelial cells in capillary-like vessel structures deposited a basement membrane-like matrix at the basal side between the vessel wall and the alginate-collagen matrix. After transplantation of the printed constructs into the chicken chorioallantoic membrane (CAM) the printed vessels connected to the CAM blood vessels and get perfused in vivo. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.},
  language  = {en}
}
@article{LuetkensErguenHuflageetal.2021,
  author    = {Luetkens, Karsten Sebastian and Erg{\"u}n, S{\"u}leyman and Huflage, Henner and Kunz, Andreas Steven and Gietzen, Carsten Herbert and Conrads, Nora and Pennig, Lenhard and Goertz, Lukas and Bley, Thorsten Alexander and Gassenmaier, Tobias and Grunz, Jan-Peter},
  title     = {Dose reduction potential in cone-beam CT imaging of upper extremity joints with a twin robotic x-ray system},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-99748-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270429},
  year      = {2021},
  abstract  = {Cone-beam computed tomography is a powerful tool for 3D imaging of the appendicular skeleton, facilitating detailed visualization of bone microarchitecture. This study evaluated various combinations of acquisition and reconstruction parameters for the cone-beam CT mode of a twin robotic x-ray system in cadaveric wrist and elbow scans, aiming to define the best possible trade-off between image quality and radiation dose. Images were acquired with different combinations of tube voltage and tube current-time product, resulting in five scan protocols with varying volume CT dose indices: full-dose (FD; 17.4 mGy), low-dose (LD; 4.5 mGy), ultra-low-dose (ULD; 1.15 mGy), modulated low-dose (mLD; 0.6 mGy) and modulated ultra-low-dose (mULD; 0.29 mGy). Each set of projection data was reconstructed with three convolution kernels (very sharp [Ur77], sharp [Br69], intermediate [Br62]). Five radiologists subjectively assessed the image quality of cortical bone, cancellous bone and soft tissue using seven-point scales. Irrespective of the reconstruction kernel, overall image quality of every FD, LD and ULD scan was deemed suitable for diagnostic use in contrast to mLD (very sharp/sharp/intermediate: 60/55/70\%) and mULD (0/3/5\%). Superior depiction of cortical and cancellous bone was achieved in FD\(_{Ur77}\) and LD\(_{Ur77}\) examinations (p < 0.001) with LD\(_{Ur77}\) scans also providing favorable bone visualization compared to FD\(_{Br69}\) and FD\(_{Br62}\) (p < 0.001). Fleiss' kappa was 0.618 (0.594-0.641; p < 0.001), indicating substantial interrater reliability. In this study, we demonstrate that considerable dose reduction can be realized while maintaining diagnostic image quality in upper extremity joint scans with the cone-beam CT mode of a twin robotic x-ray system. Application of sharper convolution kernels for image reconstruction facilitates superior display of bone microarchitecture.},
  language  = {en}
}
@phdthesis{Ipek2021,
  author    = {Ipek, Rojda},
  title     = {Einfluss der murinen Anti-CD52-Antik{\"o}rper-Therapie auf die Neurodegeneration in der chronischen MP4-induzierten experimentellen autoimmunen Enzephalomyelitis als Mausmodell der Multiplen Sklerose},
  doi       = {10.25972/OPUS-22576},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225766},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Multiple Sklerose (MS) ist eine chronisch-entz{\"u}ndliche Autoimmunerkrankung des zentralen Nervensystems (ZNS) und stellt die h{\"a}ufigste Ursache fr{\"u}hzeitiger Behinderung junger Erwachsener dar. Kennzeichnend sind multifokale ZNS-L{\"a}sionen, die durch Inflammation, Demyelinisierung und Axonsch{\"a}den gepr{\"a}gt sind und zu multiplen neurologischen Defiziten f{\"u}hren. Derzeit ist es mithilfe der verlaufsmodifizierenden Therapie m{\"o}glich, die Immunantwort abzuschw{\"a}chen und damit die Krankheitsprogression zu verz{\"o}gern. Geheilt werden kann die Erkrankung jedoch bislang nicht. Dabei ist nicht hinreichend gekl{\"a}rt, ob die neuen Therapieoptionen {\"u}ber die Immunmodulation/-suppression hinaus einen anhaltenden Schutz vor der langfristigen Neurodegeneration bieten. Basierend auf den vielversprechenden Ergebnissen klinischer Studien zur Therapie der schubf{\"o}rmig-remittierenden MS mit dem Anti-CD52-Antik{\"o}rper Alemtuzumab, der zu einer Depletion CD52-exprimierender Immunzellen f{\"u}hrt, wurden diesbez{\"u}glich Analysen in MS-Tiermodellen durchgef{\"u}hrt. Da die Untersuchung der zugrunde liegenden Patho- und Effektormechanismen am Menschen kaum m{\"o}glich ist, ist die MS-Forschung f{\"u}r ein tiefergehendes Verst{\"a}ndnis auf Tiermodelle angewiesen. Die experimentelle autoimmune Enzephalomyelitis (EAE) ist hierbei das am weitesten verbreitete Modell der MS, wof{\"u}r vor allem der C57BL/6 (B6) -Mausstamm verwendet wird, da auf diesem Hintergrund die meisten genmodifizierten M{\"a}use gez{\"u}chtet werden. Jene tierexperimentellen Studien, in denen ein muriner Anti-CD52-Antik{\"o}rper im fr{\"u}hen Krankheitsstadium der EAE (Auftreten erster paralytischer Symptome) verabreicht wurde, erbrachten den Hinweis einer neuroprotektiven und scheinbar regenerativen Wirkung des Antik{\"o}rpers. {\"U}ber einen neuroprotektiven Effekt von Alemtuzumab im schwer behandelbaren chronisch-progredienten Stadium der MS ist jedoch wenig bekannt. Die vorliegende Arbeit ist die erste detaillierte Untersuchung zum Einfluss des murinen Anti-CD52-Antik{\"o}rpers auf die Demyelinisierung, den Axonschaden und die Hirnatrophie in der MP4-induzierten EAE der B6-Maus im chronischen Verlauf der Erkrankung (ab stabilem Plateau der klinischen Symptomatik). MP4 ist ein Myelinfusionsprotein aus MBP (Myelin-Basisches-Protein) und PLP (Proteolipidprotein), welches in B6-M{\"a}usen durch aktive Immunisierung eine EAE induziert, die chronisch verl{\"a}uft und als eines von wenigen Modellen neben der T-Zell-Abh{\"a}ngigkeit die an Bedeutung zunehmende B-Zell-Komponente der MS darstellt. Histopathologisch finden sich in der chronischen MP4-induzierten EAE eine ausgepr{\"a}gte R{\"u}ckenmarks- und Kleinhirnsch{\"a}digung, die vor allem im Kleinhirn durch eine B-Zell-Aggregation charakterisiert ist. Nachdem die MP4-immunisierten M{\"a}use im chronischen Stadium der EAE an f{\"u}nf aufeinanderfolgenden Tagen mit 10 mg/kg K{\"o}rpergewicht murinem Anti-CD52-spezifischem IgG2a-Isotypantik{\"o}rper bzw. murinem unspezifischem IgG2a-Isotyp-Kontroll-Antik{\"o}rper behandelt worden waren, wurde die Lymphozytendepletion im peripheren Blut durchflusszytometrisch ermittelt und deren Einfluss auf MP4-spezifische Antik{\"o}rper anhand eines indirekten Enzyme-linked Immunosorbent Assays (ELISAs) untersucht. Als Marker f{\"u}r Axonsch{\"a}den wurde im Serum vorhandenes phosphoryliertes Neurofilament-Heavy (pNF-H) mithilfe eines indirekten Sandwich-ELISAs quantitativ bestimmt. R{\"u}ckenmark und Kleinhirn wurden ultrastrukturell auf Ver{\"a}nderungen der Myelinisierung (mittels g-Ratio: Axondurchmesser geteilt durch Gesamtdurchmesser der Nervenfaser) und auf Axonpathologien (verringerter Abstand benachbarter Neurofilamente, axolytische Axone, axonaler Verlust) untersucht. Die Hirnatrophie wurde MRT-basiert gemessen und der klinische Verlauf t{\"a}glich evaluiert. Durch die Anti-CD52-Antik{\"o}rperbehandlung wurde die T- und B-Zellzahl zwar drastisch vermindert, die MP4-spezifische Antik{\"o}rperproduktion blieb davon jedoch unbeeintr{\"a}chtigt. Ein g{\"u}nstiger Effekt auf die De- und Remyelinisierung war nicht festzustellen. Das Hirnvolumen und die klinische Pr{\"a}sentation der M{\"a}use blieben ebenfalls unver{\"a}ndert. W{\"a}hrend kein Unterschied der pNF-H-Konzentration zu erkennen war, konnte ultrastrukturell jedoch ein geringerer Axonschaden nachgewiesen werden. Insgesamt legen diese Ergebnisse nahe, dass der Anti-CD52-Antik{\"o}rper im chronischen Verlauf der EAE/MS wenig Einfluss auf die neurodegenerativen Prozesse nimmt und die Regeneration nicht f{\"o}rdern kann. Die Ursache liegt vermutlich in der Undurchl{\"a}ssigkeit der Bluthirnschranke f{\"u}r Antik{\"o}rper sowie dem limitierten Verst{\"a}ndnis der Antik{\"o}rperwirkung im ZNS. Die vorliegende Studie regt somit zur Etablierung von ZNS-wirksamen Antik{\"o}rpern an und unterstreicht die Bedeutung der Entwicklung von selektiveren neuroprotektiven und remyelinisierungsf{\"o}rdernden Behandlungsans{\"a}tzen, die eine wertvolle Erg{\"a}nzung zur verlaufsmodifizierenden Therapie darstellen k{\"o}nnten.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@phdthesis{Reeh2021,
  author    = {Reeh, Laurens},
  title     = {Immunmodulatorische Effekte CD44-positiver Gef{\"a}ßwand-residenter Stamm- und Vorl{\"a}uferzellen im myokardialen Gewebe},
  doi       = {10.25972/OPUS-25102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251020},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Identifizierung endogener Stammzellen mit kardiogenem Potenzial und die M{\"o}glichkeit, deren Differenzierung zu steuern, w{\"u}rde einen Meilenstein in der kardioregenerativen Therapie darstellen. Innerhalb der Gef{\"a}ßwand konnten unterschiedliche Stamm- und Vorl{\"a}uferzellen identifiziert werden, die sog. Gef{\"a}ßwand-residenten Stammzellen (VW-SCs). Zuletzt konnten aus CD34(+) VW-SCs, ohne genetische Manipulation, Kardiomyozyten generiert werden. Zus{\"a}tzlich fungiert die Gef{\"a}ßwand als Quelle inflammatorischer Zellen, die essenziell f{\"u}r die kardiogene Differenzierung der VW-SCs zu sein scheinen. Ziel dieser Arbeit war es, das Verhalten von CD44(+) VW-SCs zu untersuchen, um herauszufinden, inwieweit dieser Stammzelltyp eine endogene Generierung von Kardiomyozyten unterst{\"u}tzen k{\"o}nnte. Dabei wurde mit infarzierten M{\"a}useherzen, dem Aortenringassay (ARA) und dem kardialen Angiogeneseassay (CAA) gearbeitet. Sowohl in vivo in isch{\"a}mischen Arealen infarzierter M{\"a}useherzen als auch ex vivo im CAA kam es zu einem signifikanten Anstieg von CD44(+) Zellen. Mittels F{\"a}rbungen auf CD44 und Ki-67 konnte die Teilungsf{\"a}higkeit dieser Zellen demonstriert werden. Ex vivo ließen sich aus CD44(+) Zellen F4/80(+) Makrophagen generieren. Die CD44(+) VW-SCs k{\"o}nnen sich dabei sowohl zu pro-inflammatorischen iNOS(+) M1- als auch zu anti-inflammatorischen IL-10(+) M2-Makrophagen differenzieren. Eine Modulation der kardialen Inflammation k{\"o}nnte einen entscheidenden Einfluss auf die Kardiomyogenese haben. Unter VEGF-A kam es im CAA zu einer deutlichen Zunahme von CD44(+) Zellen. Unter Lenvatinib blieb das kardiale Sprouting g{\"a}nzlich aus, die Anzahl der CD44(+) Zellen stagnierte und die VW-SCs verblieben in ihren physiologischen Nischen innerhalb der Gef{\"a}ßwand. Warum es nach einem MI kaum zu einer funktionellen Herzmuskelregeneration kommt, ist weiterhin unklar. Die therapeutische Beeinflussung koronaradventitieller CD44(+) VW-SCs und inflammatorischer Prozesse k{\"o}nnte dabei zuk{\"u}nftig eine wichtige therapeutische Option darstellen.},
  subject      = {Antigen CD44},
  language  = {de}
}