Impaired immunomodulatory ability of type 2 diabetic adipose-derived mesenchymal stem cells in regulation of inflammatory condition in mixed leukocyte reaction
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Date
2019-09-23
Authors
Aliakbari, Sara
Mohammadi, Mobin
Rezaee, Mohammad Ali
Amini, Abbas Ali
Fakhari, Shohreh
Rahmani, Mohammad Reza
Journal Title
Journal ISSN
Volume Title
Publisher
Alternative Title(s)
Abstract
The immunomodulatory properties of type 2 diabetic patients’ adipose-derived mesenchymal stem cells (D-ASCs)
has not been extensively studied. In this study, we compared the immunomodulatory properties of D-ASCs and
non-diabetic subjects mesenchymal stem cells (ND-ASCs)
in co-culture with mixed
leukocyte reaction (MLR).
ASCs were isolated from adipose tissue samples of type 2 diabetic and non-diabetic subjects (age: 40-55). D-ASCs
and ND-ASCs were co-cultured with two-way MLR. Peri
pheral blood mononuclear ce
lls (PBMCs) proliferation
ratio, protein levels of IFN-
γ
and IL-10, mRNA expression of
COX-2
,
TNF-
α
,
TGF-
β
1
and
IL-6
genes in MLR,
D-ASCs and ND-ASCs co-cultures were assessed using XTT, ELISA and Real-time qRT-PCR, respectively.
PBMCs proliferation on days 2 and 4 of D-ASCs co-culture was higher than ND-ASCs co-culture of the same
days (
p
< 0.001). IFN-
γ
level decreased on day 4 compared to day 2 of ND-ASCs co-culture, but its level had not
changed in D-ASCs co-culture.
COX-2
expression on days 2 and 4 of D-ASCs co-culture was lower than ND-
ASCs co-culture of the same days (
p
< 0.05). The expression of
TNF-
α
and
IL-6
on days 2 and 4 of D-ASCs co-
culture were higher than ND-ASCs co-culture of the same days (
p
< 0.001).
TGF-
β
1
on day 4 of ND-ASCs co-
culture showed a slightly higher expression than D-ASCs co-culture of the same day. Lower suppression of
PBMCs proliferation, declined expre
ssion of anti-inflammatory and upregulated expression of pro-inflammatory
factors in D-ASCs co-culture, indicated an impairment of
these cells in modulation of the inflammatory condition.
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Keywords
Type 2 diabetes, Immunomodulation, Mesenchymal stem cells, Adipose tissue, Inflammation