Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells – a potential mechanism for targeting liver anti-fibrotic therapeutics

Elrick, Lucy J.; Leel, Valerie Hilda Marie Duncan; Blaylock, Morgan Graeme; Duncan, Linda; Drever, Matthew Ross; Strachan, Gillian; Charlton, Keith A.; Koruth, Matthew; Porter, A.J.; Wright, Matthew C.

doi:10.1016/j.jhep.2005.01.028

Cited by 34 publications

(33 citation statements)

References 29 publications

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“…They have also been shown to inactivate and acquire a quiescent-like phenotype, which might help with regression of liver fibrosis [114,115]. As well, blockage of certain proteins in HSC activation pathways might prove to have therapeutic implication in human diseases [98,[116][117][118]. Mouse model studies and advanced HSC isolation techniques have contributed to the elucidation of this cell's functions.…”

Section: Discussionmentioning

confidence: 99%

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Human hepatic stellate cell isolation and characterization

et al. 2017

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The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Significant understanding of HSCs has been achieved using rodent models and isolated murine HSCs; as well as investigating human liver tissues and human HSCs. There is growing interest and need of translating rodent study findings to human HSCs and human liver diseases. However, species-related differences impose challenges on the translational research. In this review, we focus on the current information on human HSCs isolation methods, human HSCs markers, and established human HSC cell lines.

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Section: Discussionmentioning

confidence: 99%

“…This neural marker was present in perisinusoidal HSCs in human normal liver biopsies, and increased in pathological conditions such as chronic biliary disease and chronic hepatitis C [69,97,98].…”

Section: Syn (Synaptophysin)mentioning

confidence: 97%

Human hepatic stellate cell isolation and characterization

et al. 2017

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“…The first approach was to exploit the fact that HMs express significantly higher levels of the protein synaptophysin on their cell membrane compared to qHSCs [36]. Phage display was used to generate a human recombinant single-chain antibody (scAb), C1-3 that binds to synaptophysin on the surface of HMs [37]. Fluorescent labeled C1-3 was shown to co-localize with α-sma+ HMs but not ED1+ macrophages or hepatocytes.…”

Section: Reduce Adverse Effectsmentioning

confidence: 99%

Stellate Cell Depletion Models

Oakley

Mann

2015

Stellate Cells in Health and Disease

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“…The polyhistidine tagged recombinant scAbs -C1-3 (to synaptophysin) and CSBD9 (to microcystin-LR [22] and used as a control in these studies) were expressed in Escherichia coli and purified by nickel chromatography and gel filtration essentially as previously described [20,22]. Endotoxin was removed from preparations using Q Maxi H columns (Sartorius Vivascience, Epsom, UK) and all preparations were tested (<0.2 EU/ml) by Lonza Biologics (Slough, UK) prior to use in vivo.…”

Section: Recombinant Scab Expression and Conjugationmentioning

confidence: 99%

“…Synaptophysin's external cellular location and cycling to intracellular location(s) make it a potential site for targeting liver myofibroblasts with therapeutics. Recombinant human monoclonal single chain antibodies (scAbs) were therefore generated to a conserved peptide sequence present in an extracellular domain of synaptophysin [20].…”

Section: Introductionmentioning

confidence: 99%