In vivo transformation of pancreatic acinar cells into insulin-producing cells

A technology of acinar cells and insulin, applied in the field of mammals, including human beings, can solve the problem of not achieving long-term treatment of diabetes.

Inactive Publication Date: 2009-11-04
BAYLOR RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, long-term treatment of diabetic conditions has not been achieved by providing patients with intravenous injections of betacellulin protein

Method used

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  • In vivo transformation of pancreatic acinar cells into insulin-producing cells
  • In vivo transformation of pancreatic acinar cells into insulin-producing cells
  • In vivo transformation of pancreatic acinar cells into insulin-producing cells

Examples

Experimental program
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Effect test

Embodiment 1

[0065] Example 1. Gene therapy with PDX1 and BTC produces islet-like clusters containing predominantly α-cells that disappear by day 30. The ability to convert acinar cells into glucose-responsive insulin-producing cells was shown for the first time to harness the ability of UTMD with BTC and PDX1 to regenerate normal islet function. UTMD provides an in vivo non-invasive method to detect candidate genes for islet regeneration in adult animal models of diabetes.

[0066] Animal Protocol and UTMD. Animal studies were performed according to NIH recommendations and approval by the Committee on Experimental Animal Research. Male Sprague-Dawley rats (200-250 g) were anesthetized by intraperitoneal injection of ketamine (60 mg / kg) and xylazine (5 mg / kg). The left abdomen and neck were shaved, and polyethylene tubing (PE50, Becton Dickinson, MD) was inserted through the incision into the right internal jugular vein. In the first experiment, 24 rats received one of 5 treatments: 1. ...

Embodiment 2

[0069] Example 2. Preparation of plasmid-containing lipid-stabilized microvesicles. Lipid-stabilized microvesicles were prepared following the method described by the inventors previously (6). Briefly, 250 μl of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, Sigma, St. Louis, MO) 2.5 mg / ml of DPPE (1,2-dipalmitoyl -sn-glyceryl-3-phosphatidylethanolamine, Sigma, St.Louis, MO) 0.5mg / ml solution and 50 μl of pure glycerol were added to a 1.5ml vial containing 2 mg of dry plasmid, and 20 μg of dexamethasone ( dexamathasone) were mixed thoroughly and incubated at room temperature for 30 min. The remaining headspace was filled with perfluoropropane gas (AirProducts, Inc, Allentown, PA), followed by dental amalgamator, Vialmix TM , Bristol-Myers Squibb Medical Imaging, N. Billerica, MA) mechanically shake for 30 seconds. The average diameter and concentration of microvesicles were measured with a particle counter (Beckman Coulter Multisizer III).

[0070] Plasmid construction...

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Abstract

The present invention includes compositions and methods for transforming cells into glucose- responsive, insulin-production cells using a construct that expresses betacellulin and PDXl, e.g., transforming pancreatic acinar cells using one or more expression vectors that expressed betacellulin and PDXl using ultrasound targeted microbubble destruction (UTMD).

Description

[0001] invention technical field [0002] The present invention relates to the treatment of diabetes, and more particularly, to compositions and methods for converting cells into glucose-responsive insulin-producing cells. Background of the invention [0003] Without limiting the scope of the invention, this background description is in relation to diabetes. Diabetes affects approximately 2 billion people worldwide and is on the rise (1). It is estimated to be the fifth leading cause of death in the world (2) and causes serious complications including cardiovascular disease, chronic kidney disease, blindness and neuropathy. [0004] Despite the availability of various drugs for the treatment of diabetes, including insulin therapy, adequate glycemic control is often difficult, in part because these drugs do not replicate normal islet glucose regulation. Therefore, new therapeutic strategies focus on replenishing the deficient normal amount of β-cells by islet transplantation ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/00C12N5/00C12N5/02C07H21/02C07H21/04
CPCA61K48/005A61K48/0025A61K48/0058C12N2830/008C12N2800/107A61P5/50A61P3/10C12N15/63C12N5/10C12N15/11
Inventor P·A·格雷贝恩陈树元
Owner BAYLOR RES INST
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