Long-Term In Vivo Monitoring of Adult-Derived Human Liver Stem/Progenitor Cells by Bioluminescence Imaging, Positron Emission Tomography, and Contrast-Enhanced Computed Tomography.
Adult-derived human liver stem/progenitor cells (ADHLSCs) have the potential to alleviate liver injury. However, the optimal delivery route and long-term biodistribution of ADHLSCs remain unclear. In this article, we used a triple fusion reporter system to determine the kinetic differences in the biodistribution of ADHLSCs following intrasplenic (IS) and intrahepatic (IH) administration in severe combined immunodeficiency/beige mice. ADHLSCs were transduced with a lentiviral vector expressing a triple fusion reporter comprising renilla luciferase, monomeric red fluorescent protein, and truncated HSV-1 thymidine kinase. The stability and duration of the transgenes, and the effects of transduction on the cell properties were evaluated in vitro. The acute retention and long-term engraftment in vivo were revealed by positron emission tomography and bioluminescence imaging (BLI), respectively, followed by histochemical analysis. We showed that ADHLSCs can be safely transduced with the triple fusion reporter. Radiolabeled ADHLSCs showed acute cell retention at the sites of injection. The IH group showed a confined BLI signal at the injection site, while the IS group displayed a dispersed distribution at the upper abdominal liver area, and a more intense signal. In conclusion, ADHLSCs could be monitored by BLI for up to 4 weeks with a spread out biodistribution following IS injection.
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Mei-Ju
MJ
Hsu
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Julie
J
Prigent
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Pierre-Edouard
PE
Dollet
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Joachim
J
Ravau
2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium .|3 NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, Université de Mons , Mons, Belgium .
Lionel
L
Larbanoix
2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium .|4 Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles , Brussels, Belgium .
Gaetan
G
Van Simaeys
5 Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Anne
A
Bol
5 Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Vincent
V
Grégoire
2 Center for Microscopy and Molecular Imaging , Gosselies, Belgium .|4 Service de Médecine Nucléaire, Hôpital Erasme, Université Libre de Bruxelles , Brussels, Belgium .
Serge
S
Goldman
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Gisèle
G
Deblandre
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Mustapha
M
Najimi
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .|6 Cliniques Universitaires Saint-Luc , Brussels, Belgium .
Etienne M
EM
Sokal
1 Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
Catherine A
CA
Lombard
D000328:Adult; D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000648:ultrastructure*; D008163:Luminescent Measurements / Q000379:methods; D008164:Luminescent Proteins / Q000737:chemistry / Q000302:isolation & purification; D051379:Mice; D049268:Positron-Emission Tomography; D013234:Stem Cells / Q000648:ultrastructure*; D014018:Tissue Distribution; D000097573:Red Fluorescent Protein
D003287:Contrast Media; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
biodistribution; cell tracking; cell transplantation; delivery route; rodent model; stem cell