Maturation of stem cell-derived beta-cells guided by the expression of urocortin 3

Talitha van der Meulen, Mark O. Huising

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Type 1 diabetes (T1D) is a devastating disease precipitated by an autoimmune response directed at the insulinproducing beta-cells of the pancreas for which no cure exists. Stem cell-derived beta-cells show great promise for a cure as they have the potential to supply unlimited numbers of cells that could be derived from a patient's own cells, thus eliminating the need for immunosuppression. Current in vitro protocols for the differentiation of stem cell-derived beta-cells can successfully generate pancreatic endoderm cells. In diabetic rodents, such cells can differentiate further along the beta-cell lineage until they are eventually capable of restoring normoglycemia. While these observations demonstrate that stem cell-derived pancreatic endoderm has the potential to differentiate into mature, glucose-responsive beta-cells, the signals that direct differentiation and maturation from pancreatic endoderm onwards remain poorly understood. In this review, we analyze the sequence of events that culminates in the formation of beta-cells during embryonic development, and we summarize how current protocols to generate beta-cells have sought to capitalize on this ontogenic template. We place particular emphasis on the current challenges and opportunities which occur in the later stages of beta-cell differentiation and maturation of transplantable stem cell-derived beta-cells. Another focus is on the question how the use of recently identified maturation markers such as urocortin 3 can be instrumental in guiding these efforts.

Original languageEnglish (US)
Pages (from-to)115-132
Number of pages18
JournalReview of Diabetic Studies
Volume11
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • CRF receptor
  • CRH receptor
  • Insulin
  • Pancreas development
  • Pancreatic beta-cell
  • Stem cell
  • Transplantation
  • Type 1 diabetes
  • UCN3
  • Urocortin 3

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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