Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-5-27
pubmed:abstractText
INTRODUCTION : The ability to expand organ-specific stem/progenitor cells is critical for translational applications, although uncertainties often arise in identifying the lineage of expanded cells. Therefore, superior insights into lineage maintenance mechanisms will be helpful for cell/gene therapy. METHODS : We studied epithelial cells isolated from fetal human pancreas to assess their proliferation potential, changes in lineage markers during culture, and capacity for generating insulin-expressing beta cells. Cells were isolated by immunomagnetic sorting for epithelial cell adhesion molecule (EpCAM), and characterized for islet-associated transcription factors, hormones, and ductal markers. Further studies were performed after modification of cells with the catalytic subunit of human telomerase reverse transcriptase (hTERT). RESULTS : Fetal pancreatic progenitor cells efficiently formed primary cultures, although their replication capacity was limited. This was overcome by introduction and expression of hTERT with a retroviral vector, which greatly enhanced cellular replication in vitro. However, we found that during culture hTERT-modified pancreatic progenitor cells switched their phenotype with gain of additional mesodermal properties. This phenotypic switching was inhibited when a pancreas-duodenal homeobox (Pdx)-1 transgene was expressed in hTERT-modified cells with a lentiviral vector, along with inductive signaling through activin A and serum deprivation. This restored endocrine properties of hTERT-modified cells in vitro. Moreover, transplantation studies in immunodeficient mice verified the capacity of these cells for expressing insulin in vivo. CONCLUSIONS : Limited replication capacity of pancreatic endocrine progenitor cells was overcome by the hTERT mechanism, which should facilitate further studies of such cells, although mechanisms regulating switches between meso-endodermal fates of expanded cells will need to be controlled for developing specific applications. The availability of hTERT-expanded fetal pancreatic endocrine progenitor cells will be helpful for studying and recapitulating stage-specific beta lineage advancement in pluripotent stem cells.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-10700229, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-10835641, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-10847584, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-10856888, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-12021244, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-12403815, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-12557149, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-12756298, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-15677631, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-15918158, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-16123344, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-16491084, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-16780202, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18157115, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18238854, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18243096, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18319302, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18398419, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-18754011, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-19287398, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-19669279, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-9040956, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-9726230, http://linkedlifedata.com/resource/pubmed/commentcorrection/20504287-9916802
pubmed:language
eng
pubmed:journal
pubmed:status
PubMed-not-MEDLINE
pubmed:issn
1757-6512
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6
pubmed:year
2010
pubmed:articleTitle
Switching of mesodermal and endodermal properties in hTERT-modified and expanded fetal human pancreatic progenitor cells.
pubmed:affiliation
Hepatology Division, Department of Medicine, Albert Einstein College of Medicine, Ullmann Bldg, Rm 625, 1300 Morris Park Avenue, Bronx, NY 10461, USA. kcheng@aecom.yu.edu.
pubmed:publicationType
Journal Article