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The Elusive Pancreatic Stem Cell

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Tissue-Specific Stem Cell Niche

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Whether pancreatic stem cells exist in the embryo or in the adult organ remains a controversial topic. Here, we review embryonic pancreas development, with a focus on the role of pancreatic multipotent progenitor cells during epithelial patterning, cell fate specification, and isletogenesis. Research efforts have recently turned to beta cell regeneration or replacement to treat T1D. Stimulating the expansion of stem or progenitor cells toward a beta cell fate in the adult pancreas, or generating new beta cells in the laboratory, are both major therapeutic goals in the treatment of Type 1 diabetes mellitus (T1D), a burdensome disease with no cure. We apply insights from progenitor cells in embryonic pancreatic development to adult beta cell neogenesis. New adult beta cells have been shown to originate endogenously via self-replication, or via transdifferentiation of other cell types, including acinar, hepatobiliary, or ductal cells. Regenerative approaches to treat diabetes have been successful in rodent models of pancreatic injury, but these regenerative mechanisms may not be conserved in the human pancreas. Bona fide stem cells may not exist in the adult pancreas, but achieving beta cell replacement in the diabetic pancreas appears possible, with recent leaps in induced pluripotent stem cell-derived beta cell technology, as well as current clinical trials of encapsulated beta cell replacement therapy. Abbreviations: Angptl8, angiopoietin like protein 8; BAC, bacterial artificial chromosome; bHLH, basic helix-loop-helix; BM, bone marrow; BrdU, bromodeoxyuridine; CAII, carbonic anhydrase II; Cpa1, carboxypeptidase 1; hESC, human embryonic stem cell; hGO, human gut organoid; Hlxb9, Homeobox HB9; iPSC, induced pluripotent stem cell; KGF, Keratinocyte Growth Factor; MODY4, maturity onset diabetes of the young; MPC, multipotent progenitor cell; MSC, mesenchymal stem cell; Ngn3, Neurogenin3; Nkx6.1, NK6 homeobox 1; PDL, Pancreatic Ductal Ligation; Pdx1, Pancreatic and duodenal homeobox 1; PP, pancreatic polypeptide; Ppx, partial pancreatectomy; RA, retinoic acid; RhoGAP, Rho GTPase Activating Protein; RIPCreERT2, Rat Insulin Promoter Cre Estrogen Receptor Tamoxifen; Sox9, sex determining region Y protein 9; STZ, streptozocin; T1D, Type 1 Diabetes; T2D, Type 2 Diabetes

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Acknowledgments

Our apologies to those whose work we were not able to cite due to space restrictions. This work was supported by JDRF 3-PDF-2014-202-A-N to CB, and NIH R01 grant DK079862 to OC.

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  1. Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvdd, Dallas, TX, 75390, USA

    Caitlin M. Braitsch & Ondine Cleaver

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Correspondence to Ondine Cleaver .

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Braitsch, C.M., Cleaver, O. (2015). The Elusive Pancreatic Stem Cell. In: Turksen, K. (eds) Tissue-Specific Stem Cell Niche. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-21705-5_6

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