title: A Novel Approach to Ultrasound-Mediated Tissue Decellularization and Intra-Hepatic Cell Delivery in Rats.
abstract: Liver transplantation is the mainstay of treatment for end stage liver diseases, including metabolic and congenital liver diseases. The number of suitable donor organs is, however, limited, and a whole-liver transplant requires complex surgery. Cell therapy, such as intra-portal hepatocytes transplantation, has been considered as a bridging therapy to liver transplantation but has shown a mixed clinical outcome with limited success, including low level of engraftment of transplanted hepatocytes. Here, we report a novel cell delivery technique in a rat model by creating a cavity inside the liver parenchyma by non-invasive high intensity focused ultrasound histotripsy. Our in vivo experimental results together with histologic observations show that direct injection of cells inside the cavity can facilitate successful uptake, proliferation and integration of the transplanted hepatocytes in the recipient liver. We were able to restore the plasma albumin level to 50% of the normal level in Nagase analbuminemic rats (serum albumin level of the Nagase rats was initially nil) by cell therapy after high intensity focused ultrasound-mediated histotripsy. We believe that this novel technique would enable the delivery of a large number of cells into the liver to restore liver function, particularly as a treatment for metabolic liver diseases. This novel method of intra-hepatic hepatocyte transplantation might be an invaluable tool for cell therapy in the future.
authors.affiliation: Department of Mechanical Engineering, University College London, London, UK.
authors.forename: Ki Joo
authors.initials: KJ
authors.lastname: Pahk
authors.affiliation: Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, UK.
authors.forename: Goran Hamid
authors.initials: GH
authors.lastname: Mohammad
authors.affiliation: Hepato-pancreatic-biliary and Liver Transplantation Surgery, Royal Free Hospital, University College London, London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Malago
authors.affiliation: Department of Mechanical Engineering, University College London, London, UK. Electronic address: n.saffari@ucl.ac.uk.
authors.forename: Nader
authors.initials: N
authors.lastname: Saffari
authors.affiliation: Institute for Liver and Digestive Health, Royal Free Hospital, University College London, London, UK; King Faisal Specialist Hospital and Research Center, Comparative Medicine Department and Organ Transplantation Center, Riyadh, Saudi Arabia.
authors.forename: Dipok Kumar
authors.initials: DK
authors.lastname: Dhar
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D022781:Hepatocytes / Q000637:transplantation*; D008099:Liver / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D051381:Rats; D059708:Ultrasonic Surgical Procedures / Q000379:methods*
keywords: Cell therapy; Decellularization; High intensity focused ultrasound; Histotripsy