Related Experiment Video
Updated: Mar 16, 2026
Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
Study on AAV-mediated gene therapy for diabetes in humanized liver mouse to predict efficacy in humans
Haruo Hashimoto1, Tomoko Mizushima1, Tomoyuki Ogura1
1Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
Abstract:
Most in vivo studies on the conversion to insulin-producing cells with AAV carrying PDX1 gene are performed in rodents. However, there is little information regarding Adeno-associated virus (AAV) carrying PDX1 gene transduced to human liver in vivo because accidental death caused by unpredicted factors cannot be denied, such as the hypoglycemic agent troglitazone with hepatic failure. Here we aim to confirm insulin secretion from human liver transduced with AAV carrying PDX1 gene in vivo and any secondary effect using a humanized liver mouse. As the results, AAV2-PG succeeded to improve the hyperglycemia of STZ-induced diabetic humanized liver mice. Then, the analysis of humanized liver mice revealed that the AAV2-PG was more transducible to humanized liver area than to mouse liver area. In conclusion, the humanized liver mouse model could be used to examine AAV transduction of human hepatocytes in vivo and better predict clinical transduction efficiency than nonhumanized mice.
Insights
Adeno-associated virus (AAV) carrying the PDX1 gene can improve hyperglycemia in diabetic humanized liver mice. This study demonstrates the humanized liver mouse model
Area of Science:
- Gene Therapy
- Hepatology
- Diabetes Research
Background:
- In vivo studies of PDX1 gene therapy for insulin production primarily use rodents.
- Limited data exists on Adeno-associated virus (AAV) PDX1 gene transduction in human livers due to safety concerns.
- Previous studies highlight risks associated with certain hypoglycemic agents and hepatic failure.
Purpose of the Study:
- To evaluate in vivo insulin secretion from human liver cells transduced with AAV carrying the PDX1 gene.
- To assess potential secondary effects of AAV-PDX1 gene therapy in a humanized liver mouse model.
- To determine the efficacy and safety of AAV2-PG for treating hyperglycemia in a humanized liver context.
Main Methods:
- Utilized a humanized liver mouse model to study AAV2-PG (AAV carrying PDX1 gene) transduction.
- Induced diabetes in mice using streptozotocin (STZ) to create a model for hyperglycemia.
- Assessed hyperglycemia improvement and analyzed AAV2-PG transduction efficiency in human versus mouse liver areas.
Main Results:
- AAV2-PG successfully improved hyperglycemia in STZ-induced diabetic humanized liver mice.
- Transduction efficiency of AAV2-PG was significantly higher in the humanized liver compartment compared to the native mouse liver.
- The humanized liver mouse model proved effective for evaluating AAV transduction in human hepatocytes.
Conclusions:
- The humanized liver mouse model is a valuable tool for in vivo assessment of AAV transduction efficiency in human hepatocytes.
- AAV2-PG demonstrates potential for improving hyperglycemia by enabling insulin secretion in humanized liver tissues.
- This model offers a more predictive platform for clinical AAV transduction efficiency compared to nonhumanized models.
