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

Yang，Xiao Fei1,3; Wang，Han Yue1,3,4; Lu，Wei Lin1,3; Ma，Wei1,3; Zhang，Hai2; Li，Fu Rong1,3,4

2020

American Journal of Translational Research   影响因子和分区

1943-8141

1943-8141

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.

Diabetes Hepatocyte Hydrodynamic Insulin producing cells Reprogramming UTMD

SCI

英语

第一

National Natural Science Foundation of China[81800685][81670702] ; Natural Science Foundation of Guangdong[2018A030310039][2020A1515010978] ; Science and Technology Project of Shenzhen[JCYJ20170307-100154602][JCYJ20190806150001764] ; Shenzhen Municipal Health Commission[SZX-J2017019]

Oncology ; Research & Experimental Medicine

Oncology ; Medicine, Research & Experimental

WOS:000597314100002

E-CENTURY PUBLISHING CORP

2-s2.0-85097127603

Scopus

1.Translational Medicine Collaborative Innovation Center,Southern University of Science and Technology),Shenzhen Guangdong,518020,China
2.Department of Ultrasound,Shenzhen People’s Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology),Shenzhen Guangdong,518020,China
3.Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation,Shenzhen,518020,China
4.School of Medicine,Ji’nan University,Guangzhou,510632,China

Yang，Xiao Fei,Wang，Han Yue,Lu，Wei Lin,et al. Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery[J]. American Journal of Translational Research,2020,12(11):7275-+.

Yang，Xiao Fei,Wang，Han Yue,Lu，Wei Lin,Ma，Wei,Zhang，Hai,&Li，Fu Rong.(2020).Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery.American Journal of Translational Research,12(11),7275-+.

Yang，Xiao Fei,et al."Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery".American Journal of Translational Research 12.11(2020):7275-+.