The direct differentiation of induced pluripotent stem cells derived from somatic
cells and pancreatic progenitor cells could generate functional β-cells that secrete insulin,
and are also glucose responsive. However, the cellular signals and interactions between
the pancreatic epithelium and its surrounding mesenchyme that govern pancreatic
specification and differentiation of endoderm into pancreatic progenitor cells and
eventually mature beta cells are not fully understood.
In this study, I examined various conditions that would direct the induced
pluripotent stem cells (iPSCs) derived from a pdx1: GFP mouse, or normal pancreatic
progenitor cells, to predominately β cell fate. It involves the “guided” differentiation of
iPSCs to a pancreatic lineage and also the use of a decellularized matrix to induce
differentiation into. A decellularized matrix may help mature β-cells since
decellularization has been shown to remove all the organ’s cells while preserving the
composition and biological activity of the extracellular matrix1. Thus, decelluarization
has several advantages: it removes cells to avoid any immune response post-implantation
and maintains the native environment and membrane components that provide cellular
growth and maturation of β-cells.
The results showed that the guided differentiation of iPSCs by activin A induced
definitive endodermal and pancreatic progenitor cells. Moreover, the decellularized
matrix increased exocrine and endocrine gene expression as compared to gelatin and
fibronectin, and assisted survival and maturation of all pancreatic cell types. Hence, this
novel approach would be useful to produce insulin-expressing β-cells that are also
glucose responsive and generate surrogate cells for diabetes therapy.
University of Minnesota M.S. thesis. Novemver 2011. Major: Stem cell biology. Advisor: James Dutton. 1 computer file (PDF); iii, 35 pages.
Boyce, Emma Jean.
The role of decellularized matrix in directing differentiation of pancreatic progenitor cells in pancreatic endocrine cell fate..
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