Dual Glyoxalase-1 and β-Klotho Gene-Activated Scaffold Reduces Methylglyoxal and Reprograms Diabetic Adipose-Derived Stem Cells: Prospects in Improved Wound Healing

被引:1
作者
Pang, Nadia [1 ]
Laiva, Ashang L. [1 ]
Sulaiman, Noof Z. [1 ]
Das, Priya [1 ]
O'Brien, Fergal J. [2 ,3 ,4 ]
Keogh, Michael B. [1 ]
机构
[1] Royal Coll Surg Ireland, Tissue Engn Res Grp Bahrain, POB 15503, Adliya, Bahrain
[2] Royal Coll Surgeons Ireland, Dept Anat & Regenerat Med, Tissue Engn Res Grp, 123 St Stephens Green, Dublin D02 YN77, Ireland
[3] Royal Coll Surgeons Ireland, Adv Mat & Bioengn Res Ctr, Dublin D02 PN40, Ireland
[4] Trinity Coll Dublin, Dublin D02 PN40, Ireland
关键词
glyoxalase-1; beta-klotho; gene-activated scaffold; methylglyoxal; stem cells rejuvenation; anti-fibrotic; matrix deposition; adipose-derived stem cells; wound healing; COLLAGEN; OVEREXPRESSION; MATRIX; REPAIR; STAGE;
D O I
10.3390/pharmaceutics16020265
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tissue engineering approaches aim to provide biocompatible scaffold supports that allow healing to progress often in healthy tissue. In diabetic foot ulcers (DFUs), hyperglycemia impedes ulcer regeneration, due to complications involving accumulations of cellular methylglyoxal (MG), a key component of oxidated stress and premature cellular aging which further limits repair. In this study, we aim to reduce MG using a collagen-chondroitin sulfate gene-activated scaffold (GAS) containing the glyoxalase-1 gene (GLO-1) to scavenge MG and anti-fibrotic beta-klotho to restore stem cell activity in diabetic adipose-derived stem cells (dADSCs). dADSCs were cultured on dual GAS constructs for 21 days in high-glucose media in vitro. Our results show that dADSCs cultured on dual GAS significantly reduced MG accumulation (-84%; p < 0.05) compared to the gene-free controls. Similar reductions in profibrotic proteins alpha-smooth muscle actin (-65%) and fibronectin (-76%; p < 0.05) were identified in dual GAS groups. Similar findings were observed in the expression of pro-scarring structural proteins collagen I (-62%), collagen IV (-70%) and collagen VII (-86%). A non-significant decrease in the expression of basement membrane protein E-cadherin (-59%) was noted; however, the dual GAS showed a significant increase in the expression of laminin (+300%). We conclude that dual GAS-containing Glo-1 and beta-klotho had a synergistic MG detoxification and anti-fibrotic role in dADSC's. This may be beneficial to provide better wound healing in DFUs by controlling the diabetic environment and rejuvenating the diabetic stem cells towards improved wound healing.
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页数:14
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