Related Experiment Video
Updated: Jul 31, 2026
Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel
Published on: June 29, 2015
The effect of MGDF on platelet function and thrombosis in animal models
1Department of Pharmacology, Amgen, Inc., Thousand Oaks, California, USA.
Abstract:
Recombinant human megakaryocyte growth and development factor (rHuMGDF) is a recombinant form of the endogenous c-mpl ligand, thrombopoietin (TPO). rHuMGDF (and c-mpl ligands in general) can produce a measurable sensitization of platelets to known platelet agonists. Our laboratory has observed this sensitization in vitro in both platelet-rich plasma and whole blood and ex vivo in platelets from animals receiving rHuMGDF. Concurrently, clear increases in the tyrosine phosphorylation of Jak2 and c-mpl receptor can be observed both in vitro and ex vivo. To assess the in vivo prothrombotic potential of rHuMGDF, a rabbit carotid artery model of cyclic flow reduction (CFR) was used. Intravenous administration of platelet-sensitizing dosages of rHuMGDF had no effect on the CFR pattern, whereas control experiments demonstrated that the CFR pattern can be modulated by both platelet sensitizing (epinephrine) and antithrombotic (aspirin and ketanserin) agents. We conclude that thrombopoiesis can be observed at dosages that do not sensitize platelets, and further, that platelet-sensitizing dosages of rHuMGDF do not necessarily enhance platelet-dependent thrombosis in this model.
Insights
Recombinant human megakaryocyte growth and development factor (rHuMGDF) can stimulate platelet production. However, even at dosages that sensitize platelets, rHuMGDF did not increase thrombosis in a rabbit carotid artery model.
Area of Science:
- Hematology
- Molecular Biology
- Pharmacology
Background:
- Recombinant human megakaryocyte growth and development factor (rHuMGDF) is a synthetic form of thrombopoietin (TPO).
- TPO and its analogs can sensitize platelets to agonists, potentially impacting hemostasis.
- The in vivo prothrombotic effects of rHuMGDF require further investigation.
Purpose of the Study:
- To evaluate the in vivo prothrombotic potential of rHuMGDF.
- To determine if platelet sensitization by rHuMGDF correlates with increased thrombosis.
- To investigate the effects of rHuMGDF on platelet signaling pathways.
Main Methods:
- Utilized a rabbit carotid artery cyclic flow reduction (CFR) model.
- Administered rHuMGDF intravenously and assessed its effect on CFR.
- Conducted in vitro and ex vivo experiments measuring platelet sensitization and tyrosine phosphorylation of Jak2 and c-mpl receptor.
Main Results:
- rHuMGDF administration did not alter the CFR pattern in rabbits.
- Platelet-sensitizing dosages of rHuMGDF did not enhance platelet-dependent thrombosis.
- Control experiments confirmed the CFR model's sensitivity to epinephrine, aspirin, and ketanserin.
- Increased tyrosine phosphorylation of Jak2 and c-mpl receptor was observed following rHuMGDF exposure.
Conclusions:
- Thrombopoiesis can be induced by rHuMGDF at doses that do not sensitize platelets.
- Platelet-sensitizing doses of rHuMGDF do not necessarily increase thrombosis in the rabbit carotid artery CFR model.
- The study suggests a dissociation between platelet sensitization and in vivo thrombotic risk for rHuMGDF.
