Artificial three-dimensional niches deconstruct pancreas development in vitro
Chiara Greggio,Filippo De Franceschi,Manuel Figueiredo-Larsen,Samy Gobaa,Adrian Ranga,Henrik Semb,Matthias P. Lutolf,Anne Grapin-Botton,Anne Grapin-Botton +8 more
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TLDR
Three-dimensional culture conditions in Matrigel are established that enable the efficient expansion of dissociated mouse embryonic pancreatic progenitors and 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.Abstract:
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.read more
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References
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Shankar Srinivas,Tomoko Watanabe,Chyuan-Sheng Lin,Chris M William,Yasuto Tanabe,Thomas M. Jessell,Frank Costantini +6 more
TL;DR: In contrast to existing lacZ reporter lines, where lacZ expression cannot easily be detected in living tissue, the EYFP and ECFP reporter strains are useful for monitoring the expression of Cre and tracing the lineage of these cells and their descendants in cultured embryos or organs.
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TL;DR: It is found that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer.