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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Transplantation
2014 ; 97
(7
): 740-7
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English Wikipedia
Cotransplantation with myeloid-derived suppressor cells protects cell
transplants: a crucial role of inducible nitric oxide synthase
#MMPMID24642686
Arakawa Y
; Qin J
; Chou HS
; Bhatt S
; Wang L
; Stuehr D
; Ghosh A
; Fung JJ
; Lu L
; Qian S
Transplantation
2014[Apr]; 97
(7
): 740-7
PMID24642686
show ga
BACKGROUND: Islet transplantation is an alternative to pancreas transplantation
to cure type 1 diabetes, but both require chronic immunosuppression, which is
often accompanied by deleterious side effects. The purpose of this study was to
explore prolongation of islet allograft survival by cotransplantation with
myeloid-derived suppressor cells (MDSCs) without requirement of immunosuppression
and determine the role of inducible nitric oxide synthase (iNOS) produced by
MDSCs in immune regulation. METHODS: Bone marrow cells were isolated from
wild-type (WT) or iNOS mice and cultured in the presence of
granulocyte-macrophage colony-stimulating factor and hepatic stellate cells
(HSCs), resulting in the generation of MDSCs. WT or iNOS MDSCs were
cotransplanted with islet allografts under the renal capsule of diabetic
recipient mice. RESULTS: Addition of HSCs into DC culture promoted generation of
MDSCs (instead of DCs). MDSCs had elevated expression of iNOS upon exposure to
IFN-? and inhibited T-cell responses in an MLR culture. Cotransplantation with WT
MDSCs markedly prolonged survival of islet allografts, which was associated with
reduced infiltration of CD8 T cells resulting from inhibited proliferative
response. These effects were significantly attenuated when MDSCs were deficient
in iNOS. Furthermore, iNOS MDSCs largely lost their ability to protect islet
allografts. CONCLUSIONS: Cotransplantation with HSC-induced MDSCs significantly
extends islet allograft survival through iNOS-mediated T-cell inhibition. The
results demonstrate the potential use of in vitro generated MDSCs as a novel
adjunctive immunotherapy for islet transplantation.