Generation of functional human pancreatic β cells in vitro

Felicia W. Pagliuca, Jeffrey R. Millman, Mads Gürtler, Michael Segel, Alana Van Dervort, Jennifer Hyoje Ryu, Quinn Peterson, Dale Greiner, Douglas A. Melton

Research output: Contribution to journalArticle

785 Citations (Scopus)

Abstract

The generation of insulin-producing pancreatic β cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here, we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem-cell-derived β cells (SC-β) express markers found in mature β cells, flux Ca2+ in response to glucose, package insulin into secretory granules, and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice.

Original languageEnglish (US)
Pages (from-to)428-439
Number of pages12
JournalCell
Volume159
Issue number2
DOIs
StatePublished - Oct 9 2014
Externally publishedYes

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Stem cells
Insulin
Glucose
Pluripotent Stem Cells
Cell Transplantation
Medical problems
Stem Cells
In Vitro Techniques
Fluxes
Secretory Vesicles
Drug Discovery
Cell- and Tissue-Based Therapy
Hyperglycemia
Transplantation
Serum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., ... Melton, D. A. (2014). Generation of functional human pancreatic β cells in vitro. Cell, 159(2), 428-439. https://doi.org/10.1016/j.cell.2014.09.040

Generation of functional human pancreatic β cells in vitro. / Pagliuca, Felicia W.; Millman, Jeffrey R.; Gürtler, Mads; Segel, Michael; Van Dervort, Alana; Ryu, Jennifer Hyoje; Peterson, Quinn; Greiner, Dale; Melton, Douglas A.

In: Cell, Vol. 159, No. 2, 09.10.2014, p. 428-439.

Research output: Contribution to journalArticle

Pagliuca, FW, Millman, JR, Gürtler, M, Segel, M, Van Dervort, A, Ryu, JH, Peterson, Q, Greiner, D & Melton, DA 2014, 'Generation of functional human pancreatic β cells in vitro', Cell, vol. 159, no. 2, pp. 428-439. https://doi.org/10.1016/j.cell.2014.09.040
Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014 Oct 9;159(2):428-439. https://doi.org/10.1016/j.cell.2014.09.040
Pagliuca, Felicia W. ; Millman, Jeffrey R. ; Gürtler, Mads ; Segel, Michael ; Van Dervort, Alana ; Ryu, Jennifer Hyoje ; Peterson, Quinn ; Greiner, Dale ; Melton, Douglas A. / Generation of functional human pancreatic β cells in vitro. In: Cell. 2014 ; Vol. 159, No. 2. pp. 428-439.
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