title: Noninvasive imaging of liver repopulation following hepatocyte transplantation.
abstract: Near infrared fluorescence (NIRF) optical imaging is a technique particularly powerful when studying in vivo processes at the molecular level in preclinical animal models. We recently demonstrated liver irradiation under the additional stimulus of partial hepatectomy as being an effective primer in the rat liver repopulation model based on hepatocyte transplantation. The purpose of this study was to assess optical imaging and the feasibility of donor cell expansion tracking in vivo using a fluorescent probe. Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with irradiation. Four days later, a partial hepatectomy was performed and wild-type (DPPIV+) hepatocytes were transplanted into recipient livers via the spleen. Repopulation by transplanted DPPIV+ hepatocytes was detected in vivo with Cy5.5-conjugated DPPIV antibody using the eXplore Optix System (GE HealthCare). Results were compared with nontransplanted control animals and transplanted animals receiving nonspecific antibody. Optical imaging detected Cy5.5-specific fluorescence in the liver region of the transplanted animals, increasing in intensity with time, representing extensive host liver repopulation within 16 weeks following transplantation. A general pattern of donor cell multiplication emerged, with an initially accelerating growth curve and later plateau phase. In contrast, no specific fluorescence was detected in the control groups. Comparison with ex vivo immunofluorescence staining of liver sections confirmed the optical imaging results. Optical imaging constitutes a potent method of assessing the longitudinal kinetics of liver repopulation in the rat transplantation model. Our results provide a basis for the future development of clinical protocols for suitable fluorescent dyes and imaging technologies.
authors.affiliation: Department of General and Visceral Surgery, University Hospital Goettingen, Goettingen, Germany. skoenig1@gwdg.de
authors.forename: Sarah
authors.initials: S
authors.lastname: Koenig
authors.forename: Petra
authors.initials: P
authors.lastname: Krause
authors.forename: Ali Seif Amir
authors.initials: AS
authors.lastname: Hosseini
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fraenk
authors.forename: Sarah
authors.initials: S
authors.lastname: Kimmina
authors.forename: Andrew Lee
authors.initials: AL
authors.lastname: Entwistle
authors.forename: Robert Michael
authors.initials: RM
authors.lastname: Hermann
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D008099:Liver / Q000166:cytology* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018819:Dipeptidyl Peptidase 4