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Immunol Lett. 2017 Aug;188:21-31. doi: 10.1016/j.imlet.2017.05.006. Epub 2017 May 12.

Immunomodulatory and protective effects of adipose tissue-derived mesenchymal stem cells in an allograft islet composite transplantation for experimental autoimmune type 1 diabetes.

Author information

1
Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2
Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
3
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4
Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
5
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
6
Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran.
7
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
8
Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran. Electronic address: tajik.n@iums.ac.ir.

Abstract

BACKGROUND:

Allogeneic islet transplantation could be an ideal alternative therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may have the potential to improve the outcome of this highly immunogenic transplant.

METHODS:

Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice.

RESULTS:

In vitro experiments of co-imbedded islets and AT-MSCs in a hydrogel revealed AT-MSCs are able to significantly increase insulin secretion. During a 32 days of post-transplant period, blood glucose monitoring showed a decrease from over 400mg/dl to less than 150mg/dl and at the end of 32 days, mice have been dissected and assessed. Graft histopathology demonstrated that hydrogel makes an artificial immune isolation site and AT-MSCs contribute greatly to the reduction of the immune cells infiltration. Analyses of mononuclear cells isolated from Mesenteric Lymph Nodes (MLNs) and spleen showed that AT-MSCs co-transplanted with allograft decreased pro-inflammatory cytokines and increased regulatory cytokines (for both MLNs and spleen) and regulatory T cells (Treg) population (only for MLNs). In addition, real time-PCR assays revealed that transcript levels of IDO, iNOS, and PDX1, significantly increased in allograft islets in the presence of AT-MSCs.

CONCLUSIONS:

according to results, this investigation indicates that AT-MSCs can be regarded as promising complementary candidates for engineered-cell therapy using hydrogel composites in islet transplantation.

KEYWORDS:

Allograft islet transplantation; Immunomodulatory and protective effects; Mesenchymal stem cells; Type 1 diabetes mellitus

PMID:
28506774
DOI:
10.1016/j.imlet.2017.05.006
[Indexed for MEDLINE]

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