Monocrotaline, an alternative to retrorsine-based hepatocyte transplantation in rodents.
Retrorsine has been used extensively to inhibit proliferation of resident hepatocytes in various transplantation models. Here we report a successful alternative to currently unavailable retrorsine that can be used in cellular transplantation models. Based on structural and molecular similarities, we investigate the use of monocrotaline (MCT) in cell transplantation studies in rodents. In this study, MCT was given to rats intraperitoneally in two injections 2 weeks apart. Two weeks after the final injection, a partial hepatectomy followed by splenic hepatocyte transplantation was performed. The results indicate that MCT, at two doses of 30 mg/kg, highly enhances liver repopulation by donor hepatocytes following partial hepatectomy and produces 15.3 +/- 4.9% liver repopulation within the first 6 weeks following transplantation. Additionally, we tested the effectiveness of MCT in a murine model. Using two injections of 50 mg/kg each, given 2 weeks apart, hepatocyte proliferation in the native liver was inhibited and subsequent oval cell transplants engrafted at 18 +/- 21.3% after 16 weeks posttransplantation. In conclusion, MCT can be used as an effective selective pressure for donor hepatocytes in cell transplantation to the liver in rodents.
Witek
Rafal P
RP
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL 32610-0275, USA.
Fisher
Samantha H
SH
Petersen
Bryon E
BE
D000818:Animals; D030801:Animals, Genetically Modified; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000637:transplantation*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016686:Monocrotaline / Q000494:pharmacology*; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; D049452:Green Fluorescent Proteins; D016686:Monocrotaline; D006003:Glycogen; D005952:Glucose-6-Phosphatase; D018819:Dipeptidyl Peptidase 4; C003300:retrorsine