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Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes.

作者信息

Jalili Reza B, Zhang Yun, Hosseini-Tabatabaei Azadeh, Kilani Ruhangiz T, Khosravi Maharlooei Mohsen, Li Yunyuan, Salimi Elizei Sanam, Warnock Garth L, Ghahary Aziz

机构信息

Department of Surgery, University of British Columbia, Vancouver, BC, Canada.

出版信息

PLoS One. 2016 Jan 14;11(1):e0146970. doi: 10.1371/journal.pone.0146970. eCollection 2016.


DOI:10.1371/journal.pone.0146970
PMID:26765526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4713151/
Abstract

Type 1 diabetes (T1D) results from autoimmune destruction of insulin producing β cells of the pancreatic islets. Curbing autoimmunity at the initiation of T1D can result in recovery of residual β cells and consequently remission of diabetes. Here we report a cell-based therapy for autoimmune diabetes in non-obese diabetic (NOD) mice using dermal fibroblasts. This was achieved by a single injection of fibroblasts, expressing the immunoregulatory molecule indoleamine 2,3 dioxygenase (IDO), into peritoneal cavity of NOD mice shortly after the onset of overt hyperglycemia. Mice were then monitored for reversal of hyperglycemia and changes in inflammatory/regulatory T cell profiles. Blood glucose levels dropped into the normal range in 82% of NOD mice after receiving IDO-expressing fibroblasts while all control mice remained diabetic. We found significantly reduced islet inflammation, increased regulatory T cells, and decreased T helper 17 cells and β cell specific autoreactive CD8+ T cells following IDO cell therapy. We further showed that some of intraperitoneal injected fibroblasts migrated to local lymph nodes and expressed co-inhibitory molecules. These findings suggest that IDO fibroblasts therapy can reinstate self-tolerance and alleviate β cell autoreactivity in NOD mice, resulting in remission of autoimmune diabetes.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/16c24abd9b9f/pone.0146970.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/49145995c8b0/pone.0146970.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/1e76d866aaa4/pone.0146970.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/258da89c636f/pone.0146970.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/aca8a1e38cb4/pone.0146970.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/09d2178fc3f1/pone.0146970.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/209603c1a9c4/pone.0146970.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/16c24abd9b9f/pone.0146970.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/49145995c8b0/pone.0146970.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/1e76d866aaa4/pone.0146970.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/258da89c636f/pone.0146970.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/aca8a1e38cb4/pone.0146970.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/09d2178fc3f1/pone.0146970.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/209603c1a9c4/pone.0146970.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3751/4713151/16c24abd9b9f/pone.0146970.g007.jpg

相似文献

[1]
Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes.

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[2]
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[3]
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[8]
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[10]
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引用本文的文献

[1]
Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.

Cell Biosci. 2023-8-28

[2]
Autoimmunity and Cancer-Two Sides of the Same Coin.

Front Immunol. 2022

[3]
Neglected No More: Emerging Cellular Therapies in Traumatic Injury.

Stem Cell Rev Rep. 2021-8

[4]
Lymph Node Stromal Cells: Mapmakers of T Cell Immunity.

Int J Mol Sci. 2020-10-21

[5]
IL-6/IL-6R Trans-Signaling in Fibroblasts Releases Cytokines That May Be Linked to the Pathogenesis of IgG4-Related Disease.

Front Immunol. 2020

[6]
Disodium Cromolyn and Anti-podoplanin Antibodies Strongly Inhibit Growth of BHK 21/C13-derived Fibrosarcoma in a Chick Embryo Chorioallantoic Membrane Model.

In Vivo. 2018

[7]
Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model.

Cell Transplant. 2018-6-5

[8]
IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis.

Cell Transplant. 2018-5-14

本文引用的文献

[1]
Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site.

Acta Diabetol. 2015-10

[2]
Rodent versus human insulitis: why the huge disconnect?

Curr Opin Endocrinol Diabetes Obes. 2015-4

[3]
The potential of cell-based therapy for diabetes and diabetes-related vascular complications.

Curr Diab Rep. 2014-3

[4]
IDO expressing fibroblasts promote the expansion of antigen specific regulatory T cells.

Immunobiology. 2013-6-25

[5]
The potential role of dendritic cells in the therapy of Type 1 diabetes.

Immunotherapy. 2013-6

[6]
Stem cell therapy to cure type 1 diabetes: from hype to hope.

Stem Cells Transl Med. 2013-4-9

[7]
Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus.

Clin Exp Immunol. 2013-2

[8]
Indoleamine 2,3 dioxygenase and metabolic control of immune responses.

Trends Immunol. 2012-10-25

[9]
Mechanism underlying defective interferon gamma-induced IDO expression in non-obese diabetic mouse fibroblasts.

PLoS One. 2012-5-25

[10]
Antigen-specific therapeutic approaches in Type 1 diabetes.

Cold Spring Harb Perspect Med. 2012-2

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