The pancreas is comprised of an exocrine component that functions to secrete digestive enzymes, and an endocrine component that functions to regulate glucose homeostasis. See MoreThe endocrine component is made of the Islets of Langerhans, clusters of hormone-producing cells that include primarily the alpha cell (glucagon), beta cell (insulin) and delta cell (somatostatin). Insulin and glucagon are the two primary hormones that regulate glucose homeostasis by promoting either glucose absorption into tissues or glycogen conversion into glucose, respectively. Lack of functional beta cell mass through autoimmune attack or other mechanisms ultimately leads to diabetes.
The pancreas derives from the ventral foregut endoderm. During pancreas development, a series of transcription factors are induced that direct the differentiation of pancreatic progenitor cells towards their endocrine or exocrine fates. PDX-1 and NKX6.1 are critical regulators of this process and all pancreatic progenitors co-express these two transcription factors. As cells mature, transcription factors are gained or lost depending on the ultimate fate of the cell. In the adult organ, bona fide stem cells have yet to be identified and it is thought that new beta cells, for example, arise from replication of pre-existing beta cells.1 Much of the research into pancreatic cell development is focused on understanding this process.
Human embryonic or induced pluripotent stem (ES/iPS) cells provide an additional model for studying pancreas development and disease. Protocols exist for directing human pluripotent stem cells (hPSCs) towards PDX-1/NKX6.1 co-expressing pancreatic progenitor cells2,3 and more recently towards maturing insulin-producing beta cells.4,5 hPSC-derived beta cells hold great promise for treating diabetes and significant effort is being placed on identifying the key mechanisms involved in beta cell maturation.
View this workflow to learn more about efficient generation of pancreatic progenitor cells.
- Dor Y, et al. (2004) Nature 429(6987): 41-6
- Schulz TC, et al. (2012) PLoS One 7(5): e37004
- Rezania A, et al. (2013) Stem Cells 31(11): 2432-42.
- Rezania A, et al. (2014) Nat Biotechnol 32(11): 1121-33
- Pagliuca F, et al. (2014) Cell 159(2): 428-39
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Interspecies Organogenesis Generates Autologous Functional Islets
Researchers injected mouse pluripotent stem cells (PSCs) into Pdx-1-deficient rat blastocysts, they generated rat-sized pancreata composed of mouse-PSC-derived cells. Islets subsequently prepared from these mouse–rat chimeric pancreata were transplanted into mice with streptozotocin-induced diabetes. The transplanted islets successfully normalized and maintained host blood glucose levels for over 370 days in the absence of immunosuppression.Pancreatic Cell News Volume 8.04, January 31, 2017. Read full issue at