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dc.contributor.authorHuang, Yuting
dc.contributor.authorKruse, Robert L
dc.contributor.authorDing, Hui
dc.contributor.authorItani, Mohamad I
dc.contributor.authorMorrison, Jonathan
dc.contributor.authorWang, Zack Z
dc.contributor.authorSelaru, Florin M
dc.contributor.authorKumbhari, Vivek
dc.date.accessioned2021-05-07T15:18:31Z
dc.date.available2021-05-07T15:18:31Z
dc.date.issued2021-04-28
dc.identifier.urihttp://hdl.handle.net/10713/15600
dc.description.abstractThe biliary system is routinely accessed for clinical purposes via endoscopic retrograde cholangiopancreatography (ERCP). We previously pioneered ERCP-mediated hydrodynamic injection in large animal models as an innovative gene delivery approach for monogenic liver diseases. However, the procedure poses potential safety concerns related mainly to liver or biliary tree injury. Here, we sought to further define biliary hydrodynamic injection parameters that are well-tolerated in a human-sized animal model. ERCP was performed in pigs, and hydrodynamic injection carried out using a novel protocol to reduce duct wall stress. Each pig was subjected to multiple repeated injections to expedite testing and judge tolerability. Different injection parameters (volume, flow rate) and injection port diameters were tested. Vital signs were monitored throughout the procedure, and liver enzyme panels were collected pre- and post-procedure. Pigs tolerated repeated biliary hydrodynamic injections with only occasional, mild, isolated elevation in aspartate aminotransferase (AST), which returned to normal levels within one day post-injection. All other liver tests remained unchanged. No upper limit of volume tolerance was reached, which suggests the biliary tree can readily transmit fluid into the vascular space. Flow rates up to 10 mL/sec were also tolerated with minimal disturbance to vital signs and no anatomic rupture of bile ducts. Measured intrabiliary pressure was up to 150 mmHg, and fluid-filled vesicles were induced in liver histology at high flow rates, mimicking the changes in histology observed in mouse liver after hydrodynamic tail vein injection. Overall, our investigations in a human-sized pig liver using standard clinical equipment suggest that ERCP-guided hydrodynamic injection will be safely tolerated in patients. Future investigations will interrogate if higher flow rates and pressure mediate higher DNA delivery efficiencies.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0249931en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONEen_US
dc.subjectERCP-mediated hydrodynamic injectionen_US
dc.subject.meshCholangiopancreatography, Endoscopic Retrograde--methodsen_US
dc.subject.meshSwineen_US
dc.titleParameters of biliary hydrodynamic injection during endoscopic retrograde cholangio-pancreatography in pigs for applications in gene deliveryen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0249931
dc.identifier.pmid33909609
dc.source.volume16
dc.source.issue4
dc.source.beginpagee0249931
dc.source.endpage
dc.source.countryUnited States


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