Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells
Open Access
- 29 July 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (7), e6417
- https://doi.org/10.1371/journal.pone.0006417
Abstract
In-vitro expansion of functional beta cells from adult human islets is an attractive approach for generating an abundant source of cells for beta-cell replacement therapy of diabetes. Using genetic cell-lineage tracing we have recently shown that beta cells cultured from adult human islets undergo rapid dedifferentiation and proliferate for up to 16 population doublings. These cells have raised interest as potential candidates for redifferentiation into functional insulin-producing cells. Previous work has associated dedifferentiation of cultured epithelial cells with epithelial-mesenchymal transition (EMT), and suggested that EMT generates cells with stem cell properties. Here we investigated the occurrence of EMT in these cultures and assessed their stem cell potential. Using cell-lineage tracing we provide direct evidence for occurrence of EMT in cells originating from beta cells in cultures of adult human islet cells. These cells express multiple mesenchymal markers, as well as markers associated with mesenchymal stem cells (MSC). However, we do not find evidence for the ability of such cells, nor of cells in these cultures derived from a non-beta-cell origin, to significantly differentiate into mesodermal cell types. These findings constitute the first demonstration based on genetic lineage-tracing of EMT in cultured adult primary human cells, and show that EMT does not induce multipotency in cells derived from human beta cells.Keywords
This publication has 30 references indexed in Scilit:
- Acquisition of Epithelial-Mesenchymal Transition Phenotype of Gemcitabine-Resistant Pancreatic Cancer Cells Is Linked with Activation of the Notch Signaling PathwayCancer Research, 2009
- Cadherin Switching and Activation of β-Catenin Signaling Underlie Proinvasive Actions of Calcitonin-Calcitonin Receptor Axis in Prostate CancerPublished by Elsevier BV ,2009
- HES-1 Is Involved in Adaptation of Adult Human β-Cells to Proliferation In VitroDiabetes, 2008
- In Vitro Proliferation of Cells Derived From Adult Human β-Cells Revealed By Cell-Lineage TracingDiabetes, 2008
- The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem CellsCell, 2008
- Recovery from diabetes in mice by β cell regenerationJCI Insight, 2007
- Endocrine precursor cells from mouse islets are not generated by epithelial-to-mesenchymal transition of mature beta cellsMolecular and Cellular Endocrinology, 2007
- Lineage Tracing Evidence for In Vitro Dedifferentiation but Rare Proliferation of Mouse Pancreatic β-CellsDiabetes, 2007
- Intrinsic Regulators of Pancreatic β-Cell ProliferationAnnual Review of Cell and Developmental Biology, 2006
- Expansion and redifferentiation of adult human pancreatic islet cellsBiochemical and Biophysical Research Communications, 2006