Related Experiment Video
Updated: Jul 18, 2025
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy
Khan Mohammad Imran1, Jessica Gannon2, Holly A Morrison3
1Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.
Objective:
New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors.
Methods:
Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy.
Results:
Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor.
Conclusion:
This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.
Insights
Researchers developed a new large animal model for pancreatic cancer using immunocompromised pigs. This model successfully engrafted human tumors and was used to test histotripsy, a non-invasive treatment, showing promising results for pancreatic cancer therapy.
Area of Science:
- Oncology
- Biomedical Engineering
- Animal Models
Background:
- Pancreatic cancer lacks effective treatments, hindered by the absence of suitable preclinical models.
- Pigs are valuable for human-sized medical device development but cannot effectively model human tumors.
- Existing models are insufficient for evaluating novel therapeutic strategies for pancreatic cancer.
Purpose of the Study:
- To establish an orthotopic porcine model for human pancreatic cancer.
- To evaluate histotripsy as a non-invasive treatment for pancreatic cancer in this model.
- To demonstrate the utility of this large animal model for biomedical device and therapeutic development.
Main Methods:
- Developed an immunocompromised pig model (RAG2/IL2RG double-knockout).
- Engrafted Panc-1 human pancreatic cancer cells to create orthotopic tumors.
- Administered histotripsy treatment ex vivo and in vivo to assess tumor response.
Main Results:
- Successfully established and characterized human pancreatic cancer xenografts in pigs.
- Demonstrated in situ targeting and partial ablation of pancreatic tumors using histotripsy.
- Observed a reduction in tumor collagen content following histotripsy treatment.
Conclusions:
- This study introduces a robust large mammal model for pancreatic cancer research.
- Histotripsy shows potential as a non-invasive pancreatic cancer treatment, though ultrasound guidance challenges exist.
- The model can accelerate the evaluation of biomedical devices and therapies for pancreatic cancer.
