title: Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity.
abstract: OBJECTIVE
  Intraportal human islet cell grafts do not consistently and sustainably induce insulin-independency in type 1 diabetic patients. The reasons for losses in donor cells are difficult to assess in patients. This study in streptozotocin-diabetic nude rats examines whether outcome is better in an extra-hepatic site such as omentum.
  
  
  METHODS
  Intraportal and omental implants of human islet cell grafts with the same beta cell number were followed for function and cellular composition over 5 weeks. Their outcome was also compared with that of rat islet cell grafts with similar beta cell numbers but higher purity.
  
  
  RESULTS
  While all intraportal recipients of rat islet cell grafts were normoglycaemic until post-transplant (PT) week 5, none was with human islet cell grafts; loss of human implants was associated with early infiltration of natural killer and CD45R-positive cells. Human islet cell implants in omentum achieved plasma human C-peptide positivity and normoglycaemia in, respectively, nine of 13 and five of 13 recipients until PT week 5; failures were not associated with inflammatory infiltrates but with lower beta cell numbers and purity of the grafts. Observations in human and rat islet cell implants in the omentum suggest that a delayed revascularisation can interfere with their metabolic outcome. Irrespective of normalisation, human omental implants presented beta cell aggregates adjacent to alpha cells and duct cells.
  
  
  CONCLUSIONS
  In nude rats, human islet cell implants survive better in omentum than in liver, with positive influences of the number and purity of implanted beta cells. These observations can guide studies in patients.
authors.affiliation: Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Jacobs-Tulleneers-Thevissen
authors.forename: K
authors.initials: K
authors.lastname: Bartholomeus
authors.forename: K
authors.initials: K
authors.lastname: Suenens
authors.forename: I
authors.initials: I
authors.lastname: Vermeulen
authors.forename: Z
authors.initials: Z
authors.lastname: Ling
authors.forename: K H
authors.initials: KH
authors.lastname: Hellemans
authors.forename: P
authors.initials: P
authors.lastname: In't Veld
authors.forename: M
authors.initials: M
authors.lastname: Pipeleers-Marichal
authors.forename: D
authors.initials: D
authors.lastname: Pipeleers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002096:C-Peptide / Q000097:blood; D002470:Cell Survival / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000378:metabolism* / Q000601:surgery; D008297:Male; D009852:Omentum / Q000378:metabolism* / Q000601:surgery; D051381:Rats; D011923:Rats, Nude; D017208:Rats, Wistar; D014183:Transplantation, Heterologous
chemical_list: D002096:C-Peptide; D007328:Insulin
references.citation: Lancet. 2002 Dec 21-28;360(9350):2039-45
references.pmid: 12504401
references.citation: Diabetologia. 2004 Apr;47(4):660-8
references.pmid: 15298343
references.citation: J Immunol. 2009 Jul 15;183(2):1155-65
references.pmid: 19553538
references.citation: Diabetes. 2007 Jun;56(6):1544-50
references.pmid: 17400931
references.citation: Ann Clin Biochem. 1999 Sep;36 ( Pt 5):541-64
references.pmid: 10505204
references.citation: Diabetes. 2005 Jul;54(7):2060-9
references.pmid: 15983207
references.citation: Nat Med. 1998 Feb;4(2):173-80
references.pmid: 9461190
references.citation: J Clin Endocrinol Metab. 1997 Jul;82(7):2329-36
references.pmid: 9215315
references.citation: Diabetologia. 1998 Apr;41(4):452-9
references.pmid: 9562350
references.citation: Diabetes. 1999 Jan;48(1):29-33
references.pmid: 9892219
references.citation: Am J Transplant. 2003 Mar;3(3):281-5
references.pmid: 12614282
references.citation: Diabetes. 2002 May;51(5):1362-6
references.pmid: 11978631
references.citation: Ann N Y Acad Sci. 2002 Apr;958:69-76
references.pmid: 12021085
references.citation: Diabetes. 1996 Dec;45(12):1814-21
references.pmid: 8922370
references.citation: Am J Transplant. 2005 Oct;5(10):2368-77
references.pmid: 16162184
references.citation: Transplantation. 2003 Dec 15;76(11):1623-5
references.pmid: 14702535
references.citation: Br J Surg. 2008 Dec;95(12):1449-61
references.pmid: 18991254
references.citation: Diabetes. 1989 Feb;38(2):244-8
references.pmid: 2492476
references.citation: Am J Transplant. 2009 Jan;9(1):91-104
references.pmid: 19133931
references.citation: Transplantation. 1993 Sep;56(3):524-9
references.pmid: 8212144
references.citation: Diabetes. 1991 Jul;40(7):920-30
references.pmid: 2060728
references.citation: J Clin Invest. 1996 Dec 15;98(12):2805-12
references.pmid: 8981928
references.citation: Diabetologia. 2004 Jun;47(6):998-1008
references.pmid: 15184981
references.citation: Cell Transplant. 2000 Jan-Feb;9(1):11-8
references.pmid: 10784061
references.citation: Cell Transplant. 1994 Jan-Feb;3(1):49-54
references.pmid: 8162293
references.citation: Diabetologia. 1997 Oct;40(10):1152-8
references.pmid: 9349595
references.citation: Diabetes. 2004 Jun;53(6):1407-11
references.pmid: 15161741
references.citation: Pancreatology. 2002;2(2):155-62
references.pmid: 12123096
references.citation: Diabetes. 1999 Oct;48(10):1907-14
references.pmid: 10512353
references.citation: Diabetes. 2007 Sep;56(9):2295-301
references.pmid: 17563069
references.citation: Diabetes. 1991 Jul;40(7):908-19
references.pmid: 2060727
references.citation: Diabetologia. 2002 Jun;45(6):749-63
references.pmid: 12107718
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17444-9
references.pmid: 17090674
references.citation: Transplantation. 1983 Aug;36(2):181-2
references.pmid: 6410557
references.citation: J Surg Res. 2010 Jun 1;161(1):134-8
references.pmid: 19394649