New 3D method used to grow miniature pancreas
An international team of researchers from the University of Copenhagen have successfully developed an innovative 3D method to grow miniature pancreas from progenitor cells.
Their future goal is to use this model to help in the fight against diabetes. The research results has just been published in the scientific journal Development. The new method allows the cell material from mice to grow vividly in picturesque tree-like structures. Click for image in high resolution.
Professor Anne Grapin-Botton and her team at the Danish Stem Cell Centre have developed a three-dimensional culture method which enables the efficient expansion of pancreatic cells.
The new method allows the cell material from mice to grow vividly in picturesque tree-like structures. The method offers huge long term potential in producing miniature human pancreas from human stem cells.
These human miniature organs would be valuable as models to test new drugs fast and effective – and without the use of animal models.
"The new method allows the cell material to take a three-dimensional shape enabling them to multiply more freely. It’s like a plant where you use effective fertilizer, think of the laboratory like a garden and the scientist being the gardener,” says Anne Grapin-Botton.
The cells do not thrive and develop if they are alone, and a minimum of four pancreatic cells close together is required for subsequent organoid development.
“We found that the cells of the pancreas develop better in a gel in three-dimensions than when they are attached and flattened at the bottom of a culture plate. Under optimal conditions, the initial clusters of a few cells have proliferated into 40,000 cells within a week. After growing a lot, they transform into cells that make either digestive enzymes or hormones like insulin and they self-organize into branched pancreatic organoids that are amazingly similar to the pancreas.”
Anne Grapin-Botton, Professor, Danish Stem Cell Centre
The scientists used this system to discover that the cells of the pancreas are sensitive to their physical environment such as the stiffness of the gel and to contact with other cells.
The research results has just been published in the scientific journal Development.
Pancreas and diabetes connection
An effective cellular therapy for diabetes is dependent on the production of sufficient quantities of functional beta-cells. Recent studies have enabled the production of pancreatic precursors but efforts to expand these cells and differentiate them into insulin-producing beta-cells have proved a challenge.
“We think this is an important step towards the production of cells for diabetes therapy, both to produce mini-organs for drug testing and insulin-producing cells as spare parts. We show that the pancreatic cells care not only about how you feed them but need to be grown in the right physical environment. We are now trying to adapt this method to human stem cells,” adds Anne Grapin-Botton.
In the context of a cellular therapy for diabetes, methods for pancreatic progenitor expansion and subsequent differentiation into insulin-producing beta cells would be extremely valuable. Here we establish three-dimensional culture conditions in Matrigel that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the medium composition we generate either hollow spheres, which are mainly composed of pancreatic progenitors, or complex organoids that spontaneously undergo pancreatic morphogenesis and differentiation. The in vitro maintenance and expansion of pancreatic progenitors require active Notch and FGF signaling, thus recapitulating in vivo niche signaling interactions. Our experiments reveal new aspects of pancreas development, such as a community effect by which small groups of cells better maintain progenitor properties and expand more efficiently than isolated cells, as well as the requirement for three-dimensionality. Finally, growth conditions in chemically defined biomaterials pave the way for testing the biophysical and biochemical properties of the niche that sustains pancreatic progenitors.
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