Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.
belatacept
islet transplantation
rhesus anti-thymocyte globulin
xenotransplantation
Journal
Xenotransplantation
ISSN: 1399-3089
Titre abrégé: Xenotransplantation
Pays: Denmark
ID NLM: 9438793
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
13
07
2021
received:
27
05
2021
accepted:
07
09
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
28
1
2022
Statut:
ppublish
Résumé
Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion in diabetic rhesus macaques. Induction therapy consisted of either basiliximab (n = 6) or rhesus-specific anti-thymocyte globulin (rhATG, n = 6), combined with a maintenance regimen using B7 costimulation blockade, tacrolimus with a delayed transition to sirolimus, and mycophenolate mofetil. Xenografts were monitored by blood glucose levels and porcine C-peptide measurements. Of the six receiving basiliximab induction, engraftment was achieved in 4 with median graft survival of 14 days. All six receiving rhATG induction engrafted with significantly longer xenograft survival at 40.5 days (P = 0.03). These data suggest that depletional induction provides superior xenograft survival to nondepletional induction, in the setting of a costimulation blockade-based maintenance regimen.
Identifiants
pubmed: 34951057
doi: 10.1111/xen.12713
pmc: PMC8715890
mid: NIHMS1741381
doi:
Substances chimiques
Antilymphocyte Serum
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12713Subventions
Organisme : NIAID NIH HHS
ID : U01 AI090956
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201300031C
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
PLoS One. 2014 Aug 11;9(8):e104408
pubmed: 25111080
Am J Transplant. 2009 Dec;9(12):2716-26
pubmed: 19845582
Am J Transplant. 2016 Jun;16(6):1726-38
pubmed: 26705099
Transplantation. 2001 Feb 15;71(3):460-8
pubmed: 11233911
J Immunol Res. 2017;2017:8415205
pubmed: 29159187
JAMA. 2005 Feb 16;293(7):830-5
pubmed: 15713772
Transplant Proc. 2010 Jul-Aug;42(6):2102-3
pubmed: 20692418
Am J Transplant. 2012 Jul;12(7):1765-75
pubmed: 22458586
Transplantation. 2010 Dec 27;90(12):1595-601
pubmed: 20978464
Am J Transplant. 2013 Dec;13(12):3236-43
pubmed: 24119216
Am J Transplant. 2010 Apr;10(4):773-783
pubmed: 20420638
Xenotransplantation. 2014 May-Jun;21(3):221-9
pubmed: 24806830
J Clin Invest. 1996 May 1;97(9):2119-29
pubmed: 8621802
Diabetes. 2002 Jun;51(6):1779-84
pubmed: 12031965
Am J Transplant. 2015 Nov;15(11):2837-50
pubmed: 26096041
Curr Opin Organ Transplant. 2011 Dec;16(6):620-6
pubmed: 21971510
Cell Transplant. 2017 Jun 9;26(6):925-947
pubmed: 28155815
Am J Transplant. 2017 May;17(5):1182-1192
pubmed: 28097811
Curr Diab Rep. 2018 Sep 18;18(11):103
pubmed: 30229378
Cell Transplant. 2012;21(8):1791-802
pubmed: 22776064
Am J Transplant. 2014 Feb;14(2):428-37
pubmed: 24447621
Xenotransplantation. 2021 Mar;28(2):e12659
pubmed: 33155753
Genes (Basel). 2020 Jun 26;11(6):
pubmed: 32604937
Diabetes Care. 2016 Jul;39(7):1230-40
pubmed: 27208344
Am J Transplant. 2010 Sep;10(9):2082-91
pubmed: 20883542
Cell Transplant. 2017 May 9;26(5):901-911
pubmed: 27938490
Am J Transplant. 2011 Dec;11(12):2593-602
pubmed: 21883917
Lancet Diabetes Endocrinol. 2018 Jul;6(7):527-537
pubmed: 29776895
Am J Transplant. 2012 Jun;12(6):1576-83
pubmed: 22494609
Am J Transplant. 2011 May;11(5):947-57
pubmed: 21521467
Transpl Int. 2012 Dec;25(12):1257-67
pubmed: 22994802
Xenotransplantation. 2008 Jul-Aug;15(4):225-34
pubmed: 18957045
Transplantation. 2016 Nov;100(11):2288-2300
pubmed: 27490409
Am J Transplant. 2014 Oct;14(10):2275-87
pubmed: 25220221
Cytometry. 1998 Apr 15;34(2):103-12
pubmed: 9579608
Cold Spring Harb Perspect Med. 2013 Sep 01;3(9):a015503
pubmed: 24003248
Am J Transplant. 2012 Feb;12(2):322-9
pubmed: 22053751
Exp Mol Med. 2009 Nov 30;41(11):782-92
pubmed: 19641379
Nat Med. 2000 Feb;6(2):114
pubmed: 10655072
Clin Transplant. 2021 Aug;35(8):e14369
pubmed: 34021521
Leukemia. 2007 Jul;21(7):1387-94
pubmed: 17410187
Diabetes Care. 2012 Jul;35(7):1436-45
pubmed: 22723582
Genes (Basel). 2020 Jun 19;11(6):
pubmed: 32575461
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Dec;36(12):1134-40
pubmed: 22246351
Xenotransplantation. 2014 May-Jun;21(3):244-53
pubmed: 24645827
Curr Transplant Rep. 2017;4(3):193-200
pubmed: 28932650
Ann Surg. 2018 Oct;268(4):564-573
pubmed: 30048323
N Engl J Med. 2000 Jul 27;343(4):230-8
pubmed: 10911004
Am J Transplant. 2017 Oct;17(10):2531-2536
pubmed: 28397351
Nat Med. 2006 Mar;12(3):301-3
pubmed: 16491083
Arthritis Rheum. 2003 Mar;48(3):719-27
pubmed: 12632425
Nat Med. 2006 Mar;12(3):304-6
pubmed: 16501570
Endocr Rev. 2019 Apr 1;40(2):631-668
pubmed: 30541144
Xenotransplantation. 2019 Nov;26(6):e12540
pubmed: 31219218
Xenotransplantation. 2016 Jul;23(4):300-9
pubmed: 27387829
Immunol Rev. 2014 Mar;258(1):167-82
pubmed: 24517433
N Engl J Med. 2006 Nov 9;355(19):1967-77
pubmed: 17093248
Cell Transplant. 2014;23(10):1199-211
pubmed: 23635711