TY - JOUR
T1 - Epithelial-mesenchymal transition in cells expanded in vitro from lineage-traced adult human pancreatic beta cells
AU - Russ, Holger A.
AU - Ravassard, Philippe
AU - Kerr-Conte, Julie
AU - Pattou, Francois
AU - Efrat, Shimon
N1 - Funding Information:
We thank the Cell Isolation and Transplantation Centers at the University of Geneva School of Medicine, and San Raffaele Hospital, Milano, through the European Consortium for Islet Transplantation “Islets for Research” distribution program sponsored by the Juvenile Diabetes Research Foundation, and ICR Centers, sponsored by the National Institutes of Health, for human islets. We thank Ran Elkon and Shraga Schwartz for assistance with statistical analysis, and Yael Bar for helpful discussions. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Holger A. Russ.
PY - 2009/7/29
Y1 - 2009/7/29
N2 - Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.
AB - Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.
UR - https://www.scopus.com/pages/publications/68149156892
U2 - 10.1371/journal.pone.0006417
DO - 10.1371/journal.pone.0006417
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AN - SCOPUS:68149156892
SN - 1932-6203
VL - 4
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e6417
ER -
