Epithelial-mesenchymal transition in cells expanded in vitro from lineage-traced adult human pancreatic beta cells.
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.


RESULTS
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
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.
Russ
Holger A
HA
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
Ravassard
Philippe
P
Kerr-Conte
Julie
J
Pattou
Francois
F
Efrat
Shimon
S
D017667:Adipocytes / Q000166:cytology; D000328:Adult; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D017931:DNA Primers; D004847:Epithelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology*; D008648:Mesoderm / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology
D017931:DNA Primers