In vivo Optical Imaging zum Nachweis der Leberrepopulation nach Konditionierung der Empfängerleber und Hepatozytentransplantation

Noninvasive Imaging of Liver Repopulation Following Hepatocyte Transplantation

by Ali Seif Amir Hosseini
Doctoral thesis
Date of Examination:2014-06-18
Date of issue:2014-05-23
Advisor:PD Dr. Sarah König
Referee:Prof. Dr. Frauke Alves
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-4514

 

 

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Abstract

English

Near infrared fluorescence (NIRF) optical imaging is a technique particularly powerful when studying in vivo processes at the molecular level in preclinical animal models. 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 Optix MX2 System (ART, Montreal, Canada). 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.
Keywords: In vivo optical imaging; Near infrared dye Cy5.5; Irradiation; Rat liver repopulation; DPPIV
 
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