A method for the generation of human stem cell-derived alpha cells

The generation of pancreatic cell types from renewable cell sources holds promise for cell replacement therapies for diabetes. Although most effort has focused on generating pancreatic beta cells, considerable evidence indicates that glucagon secreting alpha cells are critically involved in disease progression and proper glucose control. Here we report on the generation of stem cell-derived human pancreatic alpha (SC-alpha) cells from pluripotent stem cells via a transient pre-alpha cell intermediate. These pre-alpha cells exhibit a transcriptional profile similar to mature alpha cells and although they produce proinsulin protein, they do not secrete significant amounts of processed insulin. Compound screening identified a protein kinase c activator that promotes maturation of pre-alpha cells into SC-alpha cells. The resulting SC-alpha cells do not express insulin, share an ultrastructure similar to cadaveric alpha cells, express and secrete glucagon in response to glucose and some glucagon secretagogues, and elevate blood glucose upon transplantation in mice. Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

Veres, A. (author)
Chen, L. H. (author)
Slama, M. Q. (author)
Kenty, J. H. R. (author)
Hassoun, S. (author)
Brown, M. R. (author)
Dou, Haiqiang,1984Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xdouha (author)
Duffy, C. D. (author)
Zhou, Q. (author)
Matveyenko, A. V. (author)
Tyrberg, BjörnGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology (author)
Sorhede-Winzell, M. (author)
Rorsman, Patrik,1959Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xrorpa (author)
Melton, D. A. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

By the author/editor: Peterson, Q. P.; Veres, A.; Chen, L. H.; Slama, M. Q.; Kenty, J. H. R.; Hassoun, S.; show more...; Brown, M. R.; Dou, Haiqiang, 1 ...; Duffy, C. D.; Zhou, Q.; Matveyenko, A. V ...; Tyrberg, Björn; Sorhede-Winzell, ...; Rorsman, Patrik, ...; Melton, D. A.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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