Novel 3D organotypic urothelial cell culture model for identification of new therapeutic approaches in urological infections

Schneidewind, Laila; Neumann, Thomas; Plis, Andrzej; Brückmann, Sascha; Keiser, Markus; Krüger, William; Schmidt, Christian A.

doi:10.1016/j.jcv.2020.104283

Cited by 8 publications

(23 citation statements)

References 14 publications

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“…Furthermore, they might facilitate the in vitro testing of antiviral drugs against new potential therapeutic targets. 82 In a recent experimental study, a novel 3D cell culture approach was used to study BKV pathogenesis and potential new therapeutic targets. The results favoured the involvement of the STAT3 pathway in the pathogenesis of BKV infection, and IL-11 was recognised as the potential therapeutic target.…”

Section: Therapeutic Advancesmentioning

confidence: 99%

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

Jandial

Mishra

Sandal

et al. 2021

Therapeutic Advances in Infection

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BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.

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Section: Therapeutic Advancesmentioning

confidence: 99%

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

Jandial

Mishra

Sandal

et al. 2021

Therapeutic Advances in Infection

View full text Add to dashboard Cite

show abstract

“…Additionally, novel antiviral agents for those viruses, that are not cultivable in permanent cell lines, can be tested. [6][7][8] Therefore, our study group developed an organotypic 3D cell culture model of primary urothelial cells as well as fibroblasts and established an infection with archetype BKPyV in this culture. Interestingly, during description of parts of the viral life cycle, we observed that the proliferative activity in the urothelium is significantly increasing during infection with BKPyV, while the cultures are losing differentiation.…”

Section: Interleukin 11mentioning

confidence: 99%

“…The 3D organotypic cell culture of primary urothelial cells and primary fibroblasts was cultivated strictly to our published protocol. 6 Furthermore, the study has been conducted according to the Declaration of Helsinki principles. On day 3 after initiation of the cell culture, we infected the primary urothelial cells with BKPyV-WM12…”

Section: D Cell Culture Of Urothelium As Infection Model For Archementioning

confidence: 99%

“…2,4,5 Despite the fact that a BKPyV-associated haemorrhagic cystitis can be severe and lead to patient morbidity, no causal therapy has been established yet 2,5 .Particularly, because an appropriate cell culture model for archetype virus replication is missing and therefore knowledge about the viral life cycle, too. 6…”

mentioning

confidence: 99%

“…Particularly, because an appropriate cell culture model for archetype virus replication is missing and therefore knowledge about the viral life cycle, too. 6…”

mentioning

confidence: 99%

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Targeting IL‐11 in the treatment of BK virus‐associated haemorrhagic cystitis—A promising new approach

Schneidewind

Neumann

Krüger

et al. 2020

J Cellular Molecular Medi

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The BK polyomavirus (BKPyV) has pathogenic relevance especially in immunocompromised patients. No causal therapy has been established yet. Therefore, new therapeutic targets need to be identified in experimental studies. A 3D organotypic cell culture model with primary urothelial cells and fibroblasts was used as infection model. The detection of virus replication was performed with quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) was also used for analysis. Interleukin levels were measured by enzyme‐linked immunosorbent assay (ELISA). Interestingly, the signal transducer and activator of transcription 3 (STAT3) pathway seems to be activated during infection with BKPyV, for example phosphorylated STAT3 is significantly ( P < 0.0001) elevated on day 6 following infection. Therefore, we performed ELISAs for involved interleukins in STAT3 pathway. Interleukin 11 (IL‐11) was significantly ( P = 0.026) elevated at day 9. Subsequently, 3D cultures were treated with IL‐11 neutralizing antibody. At day 9 following infection, the median virus replication rate is 4.4 × 10 6 copies/ml. The difference to replication rate without treatment was significantly lower at day 6 ( P < 0.0001) and at day 9 ( P < 0.0001), respectively. STAT3 pathways seem to be involved during BKPyV infection and need further investigation in experimental studies. A very promising target for treatment might be IL‐11.

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Urinary Tract Infections: Virus

Luciani

Mattevi

2022

Encyclopedia of Infection and Immunity

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Novel 3D organotypic urothelial cell culture model for identification of new therapeutic approaches in urological infections

Cited by 8 publications

References 14 publications

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

Targeting IL‐11 in the treatment of BK virus‐associated haemorrhagic cystitis—A promising new approach

Urinary Tract Infections: Virus

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