Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas

Abstract

The nature and even existence of adult pancreatic endocrine stem or progenitor cells is a subject of controversy in the field of beta-cell replacement for diabetes. One place to search for such cells is in the nonendocrine fraction of cells that remain after islet isolation, which consist of a mixture of epithelia and mesenchyme. Culture in G418 resulted in elimination of the mesenchymal cells, leaving a highly purified population of nonendocrine pancreatic epithelial cells (NEPECs). To evaluate their differentiation potential, NEPECs were heritably marked and transplanted under the kidney capsule of immunodeficient mice. When cotransplanted with fetal pancreatic cells, NEPECs were capable of endocrine differentiation. We found no evidence of beta-cell replication or cell fusion that could have explained the appearance of insulin positive cells from a source other than NEPECs. Nonendocrine-to-endocrine differentiation of NEPECs supports the existence of endocrine stem or progenitor cells within the epithelial compartment of the adult human pancreas.

Defining the roles of T cell membrane proteinase and CD44 in type 1 diabetes

“…These combined events promoted the recovery of the insulin-producing b cells in diabetic NOD mice with freshly developed IDDM. According to relevant recent publications (39) and in agreement with our observations, endothelial precursor stem cells rather than the b-cells themselves are the source of the regenerated, functional, b-cells.…”

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

“…Several other studies, however, report the presence of a pool, in both rodents and humans, of endocrine and non-endocrine pancreatic precursors that differentiate into cells of the β-cell lineage 6,23 . Future studies will examine the possibility that GDNF induces β-cell neogenesis and the involvement of notch signaling 24 .…”

Sustained insulin secretory response in human islets co-cultured with pancreatic duct-derived epithelial cells within a rotational cell culture system

“…Most involve the use of serum-free, growth factor-supplemented media and the reorganisation of the cells into three-dimensional, matrix-supported structures [21,24,30]. It was not the aim of the present study to encourage the production of new beta cells, and no attempt was made to alter the phenotype of the duct epithelial cells prior to the inoculation of the islet cultures.…”