Directed differentiation of progenitor cells towards an islet-cell phenotype

Abstract

Exogenous insulin administration and oral anti-diabetic drugs are the primary means of treating diabetes. However, tight glycaemic control, with its inherent risk of hypoglycaemia, is required to prevent the microvascular and macrovascular complications of the disease. While islet or pancreas transplantations offer a longer-term cure, their widespread application is not possible, primarily because of a lack of donor tissue, the burden of life-long immunosuppression, and eventual graft rejection. The rapid increase in the incidence of diabetes has promoted the search for alternative cell-based therapies. Here we review recent advances in the directed differentiation of both endocrine and non-endocrine progenitors towards an islet-like phenotype.

Keywords: Endocrine; diabetes mellitus; insulin production; islet cells; progenitor cells.

Figure 1

Transcriptional regulation of endocrine development. All pancreatic cells originate from pdx-1 positive cells. The transcription factor Ngn-3 is required for differentiation into an endocrine phenotype. Further development into alpha, beta, or delta-cells cells is closely controlled by a range of transcription factors as indicated in the Figure.

Figure 2

The process of transdifferentiation. Transdifferentiation, also referred to as lineage reprogramming, describes the conformation of one cell to an entirely different phenotype. It differs from dedifferentiation, whereby a differentiated cell reverts to its predecessor.

Figure 3

Common embryonic origin of liver and pancreatic cells. Hepatic and pancreatic cells share a common embryonic origin in the endoderm making hepatic progenitor cells an ideal source of material for directed differentiation towards a beta-cell phenotype.