Skin deep: from dermal fibroblasts to pancreatic beta cells
- 468 Downloads
Type I diabetes (T1D) is a chronic autoimmune disease caused by pancreatic β-cell destruction induced by autoantibodies and autoreactive T cells. After significant reduction of the β-cell mass, diabetes sets in and can cause significant complications. It is estimated that more than 3 million Americans have T1D, and its prevalence among young individuals is progressively rising; however, the reasons for this increase are not known. Islet transplantation is recognized as the ultimate cure for T1D, but unfortunately, the severe scarcity of available islets makes it necessary to establish alternative sources of β-cells. Our lab seeks to establish human-induced pluripotent stem cells as an unlimited, novel source of insulin-producing cells (IPCs) that are patient-specific, obviating the requirement for immunosuppression. Although several reports have emerged demonstrating successful derivation of IPCs from human pluripotent stem cells, the efficiencies of derivation are inadequate and these IPCs do not respond to glucose stimulation in vitro. We reasoned that the use of a growth factor sequestering bioscaffold and promotion of cell–cell signaling through 3D clustering would enhance the generation of functionally superior IPCs compared to those derived by 2D differentiation. Here, we discuss a novel 3D platform for the generation of highly efficient human IPCs.
KeywordsInduced pluripotent stem cells Diabetes Insulin-producing cells iPS cells 3D differentiation Pancreatic β-cells
We would like to thank Sudhanshu Raikwar for his collaboration in the development of the 2D differentiation protocol in our laboratory. This work was made possible by support from a VA Merit Award (1I01BX001125-01A1) and by the NIH/NHLBI grant 5R01HL073015-08. Dr. Kim is supported by an AHA Career Development Award. We also thank the Integrated Islet Distribution Program (IIDP) for providing us with islets used as positive controls for this study. Without the help of the Central Microscopy Core Facility at the University of Iowa, this work would not have been possible.
- 8.Rezania A, Bruin JE, Riedel MJ, Mojibian M, Asadi A, Xu J, et al. Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes. 2012;61(8):2016–29. doi: 10.2337/db11-1711.PubMedCentralCrossRefPubMedGoogle Scholar
- 9.Xie R, Everett LJ, Lim HW, Patel NA, Schug J, Kroon E, et al. Dynamic chromatin remodeling mediated by polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells. Cell Stem Cell. 2013;12(2):224–37. doi: 10.1016/j.stem.2012.11.023.PubMedCentralCrossRefPubMedGoogle Scholar
- 33.Suzuki T, Dai P, Hatakeyama T, Harada Y, Tanaka H, Yoshimura N, et al. TGF-beta signaling regulates pancreatic beta-cell proliferation through control of cell cycle regulator p27 expression. Acta histochemica et cytochemica. 2013;46(2):51–8. doi: 10.1267/ahc.12035.PubMedCentralCrossRefPubMedGoogle Scholar