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Communicate

Insulin-releasing human pancreatic beta cell lines

Details

Project TitleInsulin-releasing human pancreatic beta cell lines
Track CodeP35170
Short Description

Researchers at Ulster University have developed a number of insulin-secreting human β-cell lines. The cells are available for licence as highly functional research tools such as for diabetes drug development and disease modeling research.

Abstract

Problem Being Solved

The restricted supply of viable human islets greatly limits the opportunity for studies of ?-cell function as well as restricting the success of worldwide clinical islet transplantation programmes.

Despite the overwhelming impetus to produce such cell lines, it has proven to be extremely difficult compared with the rodent model, with slow growth, loss of differentiated function, lack of reproducibility, dependence on co-culture with trophic factors and inability to express insulin, representing just a few of the most common deficiencies reported with studies involving human insulinoma cell lines.

Although studies using rodent tumour cell lines have succeeded in mimicking many properties of fully differentiated ?-cells and have provided the foundation for many advances in ?-cell research, generation of stable human insulin-producing cell lines would provide not only a practically unlimited supply of pure insulin-secreting cells but would also represent a fundamental progression towards testing on human-derived tissue, assisting drug development, screening of ?-cell antigens and possible cellular therapy for type 1 diabetes.

Technology

 The novel cell lines, designated 1.1B4, 1.1E7 and 1.4E7 were generated by electrofusion of human ?- cells with human ductal epithelial PANC-1 cells.

The cell lines grow as monolayers in culture showing a pavemental pattern routinely observed for epithelial cells. Their human identity was confirmed by positive expression of the highly specific human mitochondrial cox-1 gene and positive reaction with various human-specific antibodies.

Cells are immortal and provide for unlimited and stable growth and function up to passage 40. Cells have retained key attributes of functional beta cells including:

  •  Acute tests showed significant insulin secretory responses to a range of glucose concentrations (5.6 – 16.7mM) with cells showing a stepwise pattern of insulin output with a 2- 3-fold insulin-secretory response over the ranges tested, with the effect potentiated (20-60%) when glucose was combined with the phosphodiesterase inhibitor IBMX.
     
  •  The amino acids leucine, KIC, alanine and arginine caused significant increases in insulin release from cells and blockade of K-ATP channels with sulphonylureas enhanced insulin release as in native beta cells.
     
  • Intestinal hormones (GIP, GLP-1 and CCK-8) all significantly enhanced insulin release in the hybrid cells.
     
  • Cells possess intact mechanisms for glucose uptake, oxidation/utilization and phosphorylation by glucokinase.
     
  •  Subscapular implantation of the 1.1B4 cell line improved
    hyperglycaemia and resulted in glucose.

Cell lines comprising D002 are available for a non-exclusive license.

Benefits/Applications

By adapting a similar approach previously utilized in the generation of rodent insulin-secreting cells (U281), Researchers at Ulster have successfully produced a series of immortal human  Beta-cells by electrofusion technology.

These cell lines are stable in culture and exhibit many functional attributes of human pancreatic Beta- cells providing for an unlimited source of human insulin producing cells for basic biochemical studies and pharmacological screening.

Publications

Guo-Parke H, McCluskey JT, Kelly C, Hamid M, McClenaghan NH, Flatt PR.2012. Configuration of electrofusion-derived human insulin-secreting cell line as pseudoislets enhances functionality and therapeutic utility. J Endocrinol. 214(3):257-65. PMID: 22685334.

McCluskey JT, Hamid M, Parke HG, McClenaghan NH, Gomis R, Flatt PR. 2011. Development and functional characterisation of insulin-releasing human pancreatic β-cell lines produced by electrofusion. J Biol Chem. Apr 22. PMID: 21515691.

Opportunity/Partnership Sought

Ulster University’s human insulin secreting b-cell lines are currently deposited with Public Health England (PHE) who act as the University’s distributer to the research community.  All orders and sales are processed directly through PHE.

Cell lines for commercial use are available under a fee bearing non-exclusive license. The inventors of this technology are able to provide valuable know-how to assist in its successful commercialisation.

 
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Posted DateOct 12, 2017 10:16 AM