title: A simple model system enabling human CD34(+) cells to undertake differentiation towards T cells.
abstract: BACKGROUND
  Channelling the development of haematopoietic progenitor cells into T lymphocytes is dependent upon a series of extrinsic prompts whose temporal and spatial sequence is critical for a productive outcome. Simple models of human progenitor cells development depend in the main on the use of xenogeneic systems which may provide some limitations to development.
  
  
  RESULTS
  Here we provide evidence that a simple model system which utilises both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum coated matrix provides a permissive environment for the development of human CD34⁺ haematopoietic cells into mature CD4⁺ or CD8⁺ T lymphocytes in the presence of Interleukin 7 (IL-7), Interleukin 15 (IL-15) and the Fms-like tyrosine kinase 3 ligand (Flt-3L). This system was used to compare the ability of CD34(+) cells to produce mature thymocytes and showed that whilst these cells derived from cord blood were able to productively differentiate into thymocytes the system was not permissive for the development of CD34(+) cells from adult peripheral blood.
  
  
  CONCLUSIONS
  Our study provides direct evidence for the capacity of human cord blood CD34(+) cells to differentiate along the T lineage in a simple human model system. Productive commitment of the CD34⁺ cells to generate T cells was found to be dependent on a three-dimensional matrix which induced the up-regulation of the Notch delta-like ligand 4 (Dll-4) by epithelial cells.
authors.affiliation: Regenerative Medicine Group, Cranfield Health, Cranfield University, Cranfield, United Kingdom. antoniolapenna@hotmail.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Lapenna
authors.forename: Christopher
authors.initials: C
authors.lastname: B-Lynch
authors.forename: Chrysa
authors.initials: C
authors.lastname: Kapeni
authors.forename: Richard
authors.initials: R
authors.lastname: Aspinall
mesh_terms: D018952:Antigens, CD34; D001773:Blood Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D061252:Feeder Cells; D005312:Fetal Blood / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology
chemical_list: D018952:Antigens, CD34
references.citation: Curr Opin Immunol. 2011 Aug;23(4):532-6
references.pmid: 21872769
references.citation: J Invest Dermatol. 2006 May;126(5):1059-70
references.pmid: 16484986
references.citation: Blood. 2001 Oct 1;98(7):2043-51
references.pmid: 11567988
references.citation: Leuk Lymphoma. 1995 Mar;17(1-2):43-50
references.pmid: 7539659
references.citation: J Exp Med. 2008 Oct 27;205(11):2515-23
references.pmid: 18824585
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9194-9
references.pmid: 15967997
references.citation: J Immunol. 1997 Feb 1;158(3):1208-16
references.pmid: 9013961
references.citation: PLoS One. 2007 Sep 19;2(9):e898
references.pmid: 17878933
references.citation: Int Immunol. 1989;1(5):471-8
references.pmid: 2489037
references.citation: J Cell Biol. 1988 Mar;106(3):761-71
references.pmid: 2450098
references.citation: Nat Immunol. 2012 Mar 19;13(4):309-10
references.pmid: 22430774
references.citation: Cytometry. 1990;11(2):231-8
references.pmid: 1690625
references.citation: Semin Immunol. 2012 Oct;24(5):309-20
references.pmid: 22559987
references.citation: Eur J Immunol. 2011 Aug;41(8):2207-16
references.pmid: 21598246
references.citation: Curr Opin Immunol. 2007 Apr;19(2):163-8
references.pmid: 17303399
references.citation: Curr Opin Immunol. 2004 Apr;16(2):174-9
references.pmid: 15023410
references.citation: J Immunol. 2006 Jan 15;176(2):730-4
references.pmid: 16393955
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9857-60
references.pmid: 7937905
references.citation: Blood. 2007 Aug 15;110(4):1161-7
references.pmid: 17456721
references.citation: Immunol Rev. 1998 Oct;165:75-86
references.pmid: 9850853
references.citation: BMC Immunol. 2011 Feb 18;12:17
references.pmid: 21332988
references.citation: Haematologica. 2011 May;96(5):646-54
references.pmid: 21330325
references.citation: Nature. 1966 Jun 11;210(5041):1118-20
references.pmid: 5336677
references.citation: Nat Immunol. 2004 Mar;5(3):247-53
references.pmid: 14985712
references.citation: N Engl J Med. 1995 Jan 19;332(3):143-9
references.pmid: 7800006
references.citation: Nature. 1988 Sep 8;335(6186):170-4
references.pmid: 2842691
references.citation: J Immunol. 2010 Jul 15;185(2):867-76
references.pmid: 20548034
references.citation: J Immunol. 2008 Dec 1;181(11):7435-6
references.pmid: 19017928
references.citation: J Exp Med. 2007 Feb 19;204(2):331-43
references.pmid: 17261636
references.citation: J Exp Med. 2008 Oct 27;205(11):2507-13
references.pmid: 18824583
references.citation: Nature. 1985 Oct 31-Nov 6;317(6040):811-3
references.pmid: 3877245
references.citation: J Exp Med. 1993 Aug 1;178(2):391-401
references.pmid: 7688021
references.citation: Clin Exp Immunol. 2010 Sep;161(3):497-503
references.pmid: 20646007
references.citation: Blood. 2008 Feb 1;111(3):1318-26
references.pmid: 17959857
references.citation: Curr Opin Immunol. 2010 Aug;22(4):500-6
references.pmid: 20650622
references.citation: J Clin Invest. 2005 Nov;115(11):3239-49
references.pmid: 16224538
references.citation: Eur J Immunol. 1982 Jul;12(7):583-7
references.pmid: 6126365
references.citation: Nat Immunol. 2012 Feb 19;13(4):412-9
references.pmid: 22344248
references.citation: Blood. 2001 Jun 15;97(12):3683-90
references.pmid: 11389003
references.citation: BMC Immunol. 2011 Mar 23;12:22
references.pmid: 21429219
references.citation: Exp Hematol. 2011 May;39(5):570-9
references.pmid: 21296124