title: Differentiation of human skin-derived precursor cells into functional islet-like insulin-producing cell clusters.
abstract: Advances in cell-replacement strategies for diabetes have focused on renewable sources of glucose-responsive, insulin-producing cells (IPCs). One of the most proper alternatives is multipotent skin-derived precursors cells (SKPs), which can be differentiated into IPCs. In this study, we reported the isolation and expansion of human skin-derived precursors (hSKPs) followed by their differentiation into IPCs in vitro, through exposure to suitable differentiation factors. The gene expression of endocrine β cell markers was analyzed by reverse transcriptase-polymerase chain reaction. In addition, insulin production was examined immunocytochemically, and insulin and C-peptide secretion were examined using enzyme-linked immunosorbent assay. Dithizone-stained cellular clusters were observed after approximately 20 d. The clusters were found to be immunoreactive to insulin and expressed multiple genes related to pancreatic β cell development and function: insulin, Pdx-1, Islet-1, NeuroD, Glut-2, Pax-4, Ngn-3, and Nkx2.2, but not to other pancreas-specific hormones such as glucagon and somatostatin. Cellular clusters were also able to secrete detectable amounts of insulin and C-peptide in a glucose dose-dependent manner. These findings suggest that human SKPs can differentiate into functional IPCs. This may offer a safer cell source for future stem cell-based therapies.
authors: Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran.
authors: Maryam
authors: M
authors: Mehrabi
authors: Kamran
authors: K
authors: Mansouri
authors: Saman
authors: S
authors: Hosseinkhani
authors: Reza
authors: R
authors: Yarani
authors: Kheirollah
authors: K
authors: Yari
authors: Mitra
authors: M
authors: Bakhtiari
authors: Ali
authors: A
authors: Mostafaie
mesh_terms: D002096:C-Peptide / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002675:Child, Preschool; D052816:Foreskin / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors
chemical_list: D002096:C-Peptide; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007328:Insulin; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D005947:Glucose
references: Diabetes. 1989 Jan;38(1):49-53
references: 2642434
references: Nat Cell Biol. 2004 Nov;6(11):1082-93
references: 15517002
references: Diabetes. 1965 Oct;14(10):619-33
references: 5318831
references: Science. 2003 Jan 17;299(5605):363
references: 12532008
references: Stem Cells. 2007 Nov;25(11):2837-44
references: 17615265
references: J Cell Physiol. 2007 Feb;210(2):498-506
references: 17111366
references: Science. 2001 May 18;292(5520):1389-94
references: 11326082
references: Am J Pathol. 2005 Jun;166(6):1781-91
references: 15920163
references: BMC Cell Biol. 2010 Jun 25;11:46
references: 20579360
references: Nat Cell Biol. 2001 Sep;3(9):778-84
references: 11533656
references: Cell Prolif. 2012 Apr;45(2):148-57
references: 22260230
references: N Engl J Med. 1993 Jun 10;328(23):1676-85
references: 8487827
references: Diabetes. 2007 Jul;56(7):1792-801
references: 17400928
references: Development. 2002 May;129(10):2447-57
references: 11973276
references: Exp Mol Med. 2012 Jan 31;44(1):26-35
references: 22020533
references: Diabetes. 2001 Aug;50(8):1691-7
references: 11473026
references: Diabetes. 2003 Jan;52(1):76-84
references: 12502496
references: Nat Biotechnol. 2006 Nov;24(11):1392-401
references: 17053790
references: Nat Med. 2000 Mar;6(3):278-82
references: 10700229
references: PLoS One. 2009 Dec 14;4(12):e8263
references: 20011593
references: Cell. 2000 Jan 7;100(1):157-68
references: 10647940
references: Differentiation. 2001 Oct;68(4-5):205-19
references: 11776473
references: Curr Biol. 2002 Jul 23;12(14):1215-20
references: 12176331
references: Diabetes. 2004 Oct;53(10):2603-9
references: 15448090
references: Stem Cells. 2009 Aug;27(8):1941-53
references: 19544426
references: Curr Opin Cell Biol. 2002 Dec;14(6):749-55
references: 12473350
references: Diabetes. 2004 Jul;53(7):1721-32
references: 15220196
references: Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):185-98
references: 17282990
references: N Engl J Med. 2000 Jul 27;343(4):230-8
references: 10911004
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8078-83
references: 12048252
references: Cell Prolif. 2009 Feb;42(1):49-62
references: 19143763
references: In Vitro Cell Dev Biol Anim. 2006 May-Jun;42(5-6):115-23
references: 16848630
references: J Clin Invest. 2003 Mar;111(6):843-50
references: 12639990
references: Diabetes. 2005 Sep;54(9):2568-75
references: 16123344
references: Stem Cells Dev. 2009 Jul-Aug;18(6):893-906
references: 18834279
references: Nat Genet. 2002 May;31(1):111-5
references: 11923875
references: Stem Cells. 2005 Jun-Jul;23(6):727-37
references: 15917469
references: Dev Biol. 1986 Apr;114(2):492-503
references: 2420663
references: Diabetes. 2000 Feb;49(2):157-62
references: 10868930
references: PLoS One. 2011;6(12):e28175
references: 22194812
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5034-9
references: 12702762
references: J Cell Sci. 2004 Jun 15;117(Pt 14):2971-81
references: 15173316