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Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery.

ABSTRACT: In animal models, hepatocytes can be reprogrammed into insulin-producing cells (IPCs) for a novel antidiabetic treatment. However, the potential for an immunologic reaction and issues with gene integration of the viral vehicle hamper system efficacy. Here, we adopted an Ultrasound Targeted Microbubble Destruction (UTMD) enhanced hydrodynamic gene delivery system in a streptozotocin induced mouse diabetic model to examine its treatment effect. After transfection by combining UTMD and hydrodynamic injection, accumulated luciferase signal was only found in the liver with optimal signal intensity. Liver function tests showed an increase in alanine aminotransferase level followed by a decrease to normal levels. Then this new gene delivery system was used to deliver Pdx1, Neurog3, and MafA plasmids into diabetic mice. We found that glucose levels gradually decreased, and insulin levels increased in transfected diabetic mice compared to controls. Glucose intolerance in transfected mice was alleviated. Gene expression assay confirmed the reprogramming of hepatocytes. We demonstrated the feasibility of repeated plasmid transfection in vivo by UTMD enhanced hydrodynamic gene delivery system.

SUBMITTER: Yang XF

PROVIDER: S-EPMC7724341 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery.

Yang Xiao-Fei XF Wang Han-Yue HY Lu Wei-Lin WL Ma Wei W Zhang Hai H Li Fu-Rong FR

American journal of translational research 20201115 11

In animal models, hepatocytes can be reprogrammed into insulin-producing cells (IPCs) for a novel antidiabetic treatment. However, the potential for an immunologic reaction and issues with gene integration of the viral vehicle hamper system efficacy. Here, we adopted an Ultrasound Targeted Microbubble Destruction (UTMD) enhanced hydrodynamic gene delivery system in a streptozotocin induced mouse diabetic model to examine its treatment effect. After transfection by combining UTMD and hydrodynamic ...[more]

PMID: 33312366

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Project description:ObjectiveTo investigate the efficacy and mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with radiotherapy (XRT) on glioblastoma.MethodsThe enhanced radiosensitization by UTMD was assessed through colony formation and cell apoptosis in Human glioblastoma cells (U87MG). Subcutaneous transplantation tumors in 24 nude mice implanted with U87MG cells were randomly assigned to 4 different treatment groups (Control, UTMD, XRT, and UTMD + XRT) based on tumor sizes (100-300 mm3). Tumor growth was observed for 10 days after treatment, and then histopathology stains (HE, CD34, and γH2AX) were applied to the tumor samples. A TUNEL staining experiment was applied to detect the apoptosis rate of mice tumor samples. Meanwhile, tissue proteins were extracted from animal specimens, and the expressions of dsDNA break repair-related proteins from animal specimens were examined by the western blot.ResultsWhen the radiotherapy dose was 4 Gy, the colony formation rate of U87MG cells in the UTMD + XRT group was 32 ± 8%, lower than the XRT group (54 ± 14%, p < 0.01). The early apoptotic rate of the UTMD + XRT group was 21.1 ± 3% at 48 h, higher than that of the XRT group (15.2 ± 4%). The tumor growth curve indicated that the tumor growth was inhibited in the UTMD + XRT group compared with other groups during 10 days of observation. In TUNEL experiment, the apoptotic cells of the UTMD + XRT group were higher than that of the XRT group (p < 0.05). The UTMD + XRT group had the lowest MVD value, but was not significantly different from other groups (p > 0.05). In addition, γH2AX increased due to the addition of UTMD to radiotherapy compared to XRT in immunohistochemistry (p < 0.05).ConclusionsOur study clearly demonstrated the enhanced destructive effect of UTMD combined with 4 Gy radiotherapy on glioblastoma. This could be partly achieved by the increased ability of DNA damage of tumor cells.

Dataset Information

Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery.

Publications

Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery.

Similar Datasets

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