Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter.
The disease diabetes mellitus arises as a consequence of a failure of the beta-cells in the islets of Langerhans of the pancreas to produce insulin in the amounts required to meet the needs of the body. Whole pancreas or islet transplants in patients with severe diabetes effectively restore insulin production. A lack of availability of donor pancreata requires the development of alternative sources of islets such as the ex vivo culture and differentiation of stem/progenitor cells. Earlier we discovered multipotential progenitor cells in islets isolated from adult human pancreata that express the neural stem cell marker nestin: nestin-positive islet-derived progenitor cells (NIPs). Recently it was shown that the exclusion of the Hoechst 33342 dye, which defines the pluripotential side population (SP) of hematopoietic stem cells, is mediated by the ATP-binding cassette transporter, ABCG2. Here we report that the human islet-derived NIPs contain a substantial subpopulation of SP cells that co-express ABCG2, MDR1, and nestin. Thus NIPs may be a potential source of adult pluripotential stem/progenitor cells useful for the production of islet tissue for transplantation into diabetic subjects.
Lechner
Andreas
A
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, and Harvard Medical School, 55 Fruit Street-WEL320, Boston, MA 02114, USA.
Leech
Colin A
CA
Abraham
Elizabeth J
EJ
Nolan
Anna L
AL
Habener
Joel F
JF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D001562:Benzimidazoles / Q000737:chemistry; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D012333:RNA, Messenger; C017807:bisbenzimide ethoxide trihydrochloride