Abstract:
:Exenatide is an analog of the incretin hormone glucagon-like peptide (GLP-1) that is used for the treatment of T2D for their metabolic effects. In addition to its insulinotropic effects, exenatide increases functional islet mass and improves their survival. Improved outcomes have been reported in recent clinical islet transplantation trials for the treatment of type 1 diabetes. The purpose of this study was to investigate whether exenatide has anti-inflammatory properties in human islets. Exenatide treatment improved islet function, significantly reduced content of inflammation-related molecules (tissue factor, IFN-γ, IL-17, IL-1β, and IL-2) and caspase 3 activation, whereas increased phosphorylation of ERK1/2, STAT3, and Akt in vitro. Immunostaining showed expression of GLP-1R in β-cells but not in α-cells. IL-1β colocalized with GLP-1R in β-cells. Induction of serine proteinase inhibitor 9 (PI-9) was detected after exposure of human islets to exenatide in vitro and after transplantation into immunodeficient mice. GLP-1 induced PI-9 expression in vitro but to a lower extent than exenatide. This effect was partially blocked by the antagonist exendin-9 in vitro. As assessed by immunostaining PI-9 is mostly expressed in β-cells but not in α-cells. In conclusion, we describe anti-inflammatory and cytoprotective properties of exenatide in human islets. Exenatide-mediated PI-9 expression, the only known granzyme B inhibitor, unveils potential immunoregulatory properties.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Cechin SR,Pérez-Álvarez I,Fenjves E,Molano RD,Pileggi A,Berggren PO,Ricordi C,Pastori RLdoi
10.3727/096368911X576027subject
Has Abstractpub_date
2012-01-01 00:00:00pages
633-48issue
4eissn
0963-6897issn
1555-3892pii
ct0342cechinjournal_volume
21pub_type
杂志文章abstract::In multiple sclerosis (MS), a chronic inflammatory relapsing demyelinating disease, failure to control or repair damage leads to progressive neurological dysfunction and neurodegeneration. Implantation of neural stem cells (NSCs) has been shown to promote repair and functional recovery in the acute experimental autoi...
journal_title:Cell transplantation
pub_type: 杂志文章
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abstract::Experiments on spinal cord injury (SCI) have largely focused on the transplantation of stem cells into injured spinal cords for motor recovery while neglecting to investigate bladder dysfunction. The present study was performed to investigate the effect of B10 human mesenchymal stem cells (hMSCs) directly transplanted...
journal_title:Cell transplantation
pub_type: 杂志文章
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abstract::Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at le...
journal_title:Cell transplantation
pub_type: 临床试验,杂志文章
doi:10.1177/096368970000900111
更新日期:2000-01-01 00:00:00
abstract::Hepatocyte transplantation (HT) has become an effective therapy for patients with metabolic inborn errors. We report the clinical outcome of four children with metabolic inborn errors that underwent HT, describing the cell infusion protocol and the metabolic outcome of transplanted patients. Cryopreserved hepatocytes...
journal_title:Cell transplantation
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abstract::Our purpose was to evaluate whether or not and when phenotypic modulation of smooth muscle cells (SMCs) in hybrid vascular prostheses preincorporated with SMCs occurs upon implantation. Two types of hybrid vascular grafts incorporated with vascular cells derived from canine jugular veins were prepared: grafts containi...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Islet transplantation as a therapy or cure for type 1 diabetes has significant promise but has been limited by islet mass requirements and long-term graft failure. The intrahepatic and intravascular site may be responsible for significant loss of transplanted islets. Nonencapsulating biomaterial scaffolds provide a st...
journal_title:Cell transplantation
pub_type: 杂志文章
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abstract::We previously demonstrated that mesenchymal cells from human amniotic membrane (hAMTCs) inhibit the generation and maturation of monocyte-derived dendritic cells (DCs) in vitro. Considering the crucial role of DCs in the immune response and that epithelial cells of the human amniotic membrane (hAECs) share some of the...
journal_title:Cell transplantation
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abstract::Potential labels for identifying embryonic raphe neurons and a clonal, neuronally differentiating, raphe-derived cell line, RN33B, in CNS transplantation studies were tested by first characterizing the labels in vitro. The labels that were tested included 4',6-diamidino-2-phenylindole hydrochloride, 1,1'-dioctadecyl-3...
journal_title:Cell transplantation
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abstract::Nerve growth factor (NGF) exerts both trophic (cell survival) and tropic (axonal growth-promoting) effects on several neuronal populations. In particular, its robust ability to prevent lesion-induced and spontaneous age-related basal forebrain cholinergic neuronal degeneration, and to promote mnemonic recovery, has su...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1177/096368970000900508
更新日期:2000-09-01 00:00:00
abstract::There are conflicting reports on the survival and immune reaction to allografts and xenografts of cultured skin substitutes (CSS). In this study, we investigated the allogeneic and xenogeneic responses to CSS of human keratinocytes and genetically engineered CSS expressing keratinocyte growth factor (KGF) that forms a...
journal_title:Cell transplantation
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更新日期:2004-01-01 00:00:00
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journal_title:Cell transplantation
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
abstract::Direct reprogramming of an adult cell into another differentiated lineage-such as fibroblasts into neurons, cardiomyocytes, or blood cells-without passage through an undifferentiated pluripotent stage is a new area of research that has recently emerged alongside stem cell technology and induced pluripotent stem cell r...
journal_title:Cell transplantation
pub_type: 杂志文章,评审
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/s0963-6897(97)00005-5
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.1016/0963-6897(96)00026-7
更新日期:1996-07-01 00:00:00
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/000000003108747343
更新日期:2003-01-01 00:00:00
abstract::Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activit...
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pub_type: 杂志文章
doi:10.3727/096368916X693022
更新日期:2017-01-24 00:00:00
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) hold great promise for bone regeneration. However, the power of mesenchymal stem cells has not been applied to structural bone allografts in clinical practice. This study designed a new strategy to enhance the efficiency of allografts for segmental bone regeneration. Isolated MSCs were cu...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368909788809839
更新日期:2009-01-01 00:00:00
abstract::Functional demands on a bioartificial liver support (BAL) device are not limited to biosynthetic activities, but must also encompass metabolic removal of potentially toxic substances. For most BALs, however, the concept and design are exclusively directed to biosynthetic support. To add the ability to metabolize and r...
journal_title:Cell transplantation
pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00
abstract::Although emerging evidence links mesenchymal stem cells (MSCs) with cancer metastasis, the underlying mechanisms are poorly understood. In the present study, we found that human umbilical cord-derived MSCs (UC-MSCs) promoted MCF-7 cell migration in vitro and metastasis in vivo. To explore the mechanisms, the character...
journal_title:Cell transplantation
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journal_title:Cell transplantation
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368912X653192
更新日期:2013-01-01 00:00:00
abstract::Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acety...
journal_title:Cell transplantation
pub_type: 杂志文章
doi:10.3727/096368911X586765
更新日期:2012-01-01 00:00:00
abstract::The diverse requirements for a successful islet encapsulation barrier suggest the benefit of a barrier system that presents differing functionalities to encapsulated cells and host cells. Initially, multifunctional hydrogels were synthesized via the sequential photopolymerization of PEG hydrogel layers, each with diff...
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pub_type: 杂志文章
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journal_title:Cell transplantation
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Airway epithelial cell injury is a key triggering event to activate allergic airway inflammation, such as asthma. We previously reported that administration of mesenchymal stem cells (MSCs) significantly alleviated allergic inflammation in a mouse model of asthma, and the mmu-miR-21/ACVR2A axis may be involved. Howeve...
journal_title:Cell transplantation
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abstract::In human neonates, immature GABAergic interneurons are markedly affected by an excitotoxic insult. While in adults the interest of cell transplantation has been demonstrated in several neurological disorders, few data are available regarding the immature brain. The low survival rate constitutes a strong limitation in ...
journal_title:Cell transplantation
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更新日期:2014-01-01 00:00:00
abstract::The biohybrid artificial pancreas is designed to enclose pancreatic tissues with a selectively permeable membrane that immunoisolates the graft from the host immune system, allowing those endocrine tissues to survive and control glucose metabolism for an extended period of time. The pancreatic B cell line MIN6 is esta...
journal_title:Cell transplantation
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更新日期:1997-09-01 00:00:00