Pancreatic endocrine progenitor cell therapies for the treatment of obesity and type 2 diabetes (T2D)

A technology of endocrine progenitor cells and type 2 diabetes, applied in the direction of pancreatic cells, endocrine system diseases, animal cells, etc., can solve problems such as treatment difficulties and lack of islets

Pending Publication Date: 2018-01-02
CCS VENTURES LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, recent treatments have included transplantation of islets of Langerhans, which suffers from a lack of transplantable islets

Method used

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  • Pancreatic endocrine progenitor cell therapies for the treatment of obesity and type 2 diabetes (T2D)
  • Pancreatic endocrine progenitor cell therapies for the treatment of obesity and type 2 diabetes (T2D)
  • Pancreatic endocrine progenitor cell therapies for the treatment of obesity and type 2 diabetes (T2D)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0197] Example 1: Development of Obesity and Type 2 Diabetes (T2D) Models in Immunodeficient Mice

[0198] For this example, 8 to 10 week old male SCID-beige mice (C.B-Igh-1b / GbmsTac-Prkdc scid -Lyst bg N7; Taconic TM , Hudson, NY) maintained on a 12-h light / dark cycle. All mice received a standard irradiated diet (Harlan Laboratories TM , Teklad Diet TM #2918, Madison, WI) for 2 weeks to allow acclimatization. Mice were placed on 4 different diets (Research Diets TM , NewBrunswick, NJ, one of USA), carried out 36 weeks of research (every diet n=11): 1) "10% fat " control diet (D12450K-10kcal% fat; 70kcal% carbohydrate, no sucrose); 2 ) "45% fat" diet (D12451-45kcal% fat, mainly lard; 35kcal% carbohydrate); 3) "60% fat" diet (D12492-60kcal% fat, mainly lard; 20kcal% carbohydrate) or 4) "Western" diet (D12079B - 41 kcal% fat, mainly milk fat; 43 kcal% carbohydrates, mainly sucrose).

[0199] Using a handheld blood glucose meter (Lifescan TM , Milpitas, California) to m...

Embodiment 2

[0202] Example 2: In Vitro Generation of Pancreatic Endocrine Progenitor Cells from Human Embryonic Stem Cells

[0203] Cells of human embryonic stem cell line H1 (WA01 cells, WiCell Research Institute TM , Madison, WI), as a single cell at 1x10 5 cells / cm 2 Inoculation to mTeSR-1 TM (Stem Cell Technologies TM , Vancouver, BC; Cat.no.05850) in a 1:30 dilution of MATRIGEL TM (Becton Dickinson BioSciences TM , Franklin Lakes, NJ; Catalog ("Cat.") No. 356231) coated dishes. At approximately 70-80% confluency, H1 cell cultures were washed with Mg2+ and Ca2+-free 1X Dulbeccos phosphate-buffered saline (Invitrogen TM , Carlsbad, CA; Cat.No.14190) washing, then at room temperature with 0.02% Versene TM ("EDTA") (Lonza TM , Walkersville, MD; Cat. No. 17-711E) for 12 min. with mTeSR-1 TM Released single cells were washed and spun at 1000 rpm for 5 min. The resulting cell pellet was resuspended in the ROCK inhibitor Y-27632 supplemented with 10 μM TM (Sigma-Aldrich TM , St....

Embodiment 3

[0211] Example 3: Exposure to HFD does not affect in vivo function of hESC-derived endocrine cells

[0212] According to the following steps, the pancreatic endocrine precursor cells of Example 2 were encapsulated in 20 μl Theracyte TM Macroencapsulation device (TheraCyte Inc. TM , Laguna Hills, CA). Will be about 5x10 6 Endocrine precursor cells (in the form of cell clusters) are placed in a positive displacement pipette. Using gentle pressure, place the capillary tip / piston tip containing the cells snugly in the center of the 24 gauge catheter and dispense the cells from the positive displacement pipette through the catheter into the device. Titanium barbs are used to seal the unit. The encapsulated pancreatic endocrine precursor cells were then transplanted subcutaneously into 7 SCID-beige mice from each of the 4 dietary regimens. All mice were anesthetized with inhalable isoflurane, and transplant recipients received approximately 5x10 6 pancreatic endocrine precurso...

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Abstract

Provided herein are therapies, and methods using that therapy, in the treatment of one or more of Type 2 diabetes (T2D), obesity, glucose intolerance and insulin resistance or to control weight gain in subjects. In particular, the subject may be candidates for treatment with one or more small molecule anti-diabetic drugs and the therapy may include implanting a population of pancreatic endocrine progenitor cells into the subject, where the cells are allowed to mature in vivo to produce a population.

Description

technical field [0001] The present invention relates to methods of treating metabolic disorders, medical conditions and related pathological conditions in a subject. In particular, the present invention relates to the use of cells differentiated from pluripotent stem cells alone or in combination with antidiabetic drugs for achieving weight loss, improved glucose tolerance and / or enhanced insulin sensitivity in a subject. [0002] Cross References to Related Applications [0003] This application claims the benefit of US Provisional Patent Application No. 62 / 131,540, filed March 11, 2015, entitled "Therapies for the Treatment of Obesity." Background of the invention [0004] Obesity is rapidly becoming a global epidemic that cuts across all ages and socioeconomic groups. The number of overweight and obese people in the world has risen from 857 million in 1980 to 2.1 billion in 2013 (Ng, et al., Global, Regional & National Prevalence of Overweight and Obesity in Children an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/39A61K31/155A61K31/4439A61K31/4985A61P3/00A61P3/10C12N5/071C07C279/26C07D417/12C07D487/04
CPCA61K45/06A61K31/155A61K31/4439A61K31/4985C12N5/0677A61K35/39A61P3/00A61P3/04A61P3/08A61P43/00A61P5/50A61P3/10
Inventor 蒂莫西·J·基弗詹尼弗·E·布鲁因
Owner CCS VENTURES LTD
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