scholarly journals The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster

2018 ◽  
Author(s):  
Takashi Kido ◽  
Shigeru Miyagawa ◽  
Takasumi Goto ◽  
Katsuto Tamai ◽  
Takayoshi Ueno ◽  
...  

AbstractObjectivesWe hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.MethodsTwenty-week-old J2N-k hamsters, which are δ-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).ResultsThe HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor α stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.ConclusionsSystemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.

2021 ◽  
Vol 12 (1) ◽  
pp. 561-572
Author(s):  
Wen Zeng ◽  
Yu Wang ◽  
Yufeng Xi ◽  
Guoqing Wei ◽  
Rong Ju

Abstract Objectives Hypoxic–ischemic brain damage (HIBD) is a major cause of brain injury in neonates. Bone marrow mesenchymal stem cells (BMSCs) show therapeutic potential for HIBD, and genetic modification may enhance their neuroprotective effects. The goal of this study was to investigate the neuroprotective effects of hepatocyte growth factor (HGF)-overexpressing BMSCs (BMSCs-HGF) against HIBD and their underlying mechanisms. Methods: BMSCs were transfected with HGF using adenoviral vectors. HIBD models were established and then BMSCs were transplanted into the brains of HIBD rats via intraventricular injection. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure cerebral infarction volumes. In vitro, primary cultured cortical neurons were co-cultured with BMSCs in a Transwell plate system. Oxygen–glucose deprivation (OGD) was applied to imitate hypoxic–ischemic insult, and PD98059 was added to the culture medium to block the phosphorylation of extracellular signal-regulated kinase (ERK). Cell apoptosis was determined using TUNEL staining. The expression of HGF was measured by immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blots. The expression of phosphorylated ERK (p-ERK) and B-cell lymphoma-2 (Bcl-2) was measured by western blots. Results HGF-gene transfection promoted BMSC proliferation. Moreover, BMSCs-HGF decreased HIBD-induced cerebral infarction volumes and enhanced the protective effects of the BMSCs against HIBD. BMSCs-HGF also increased expression of HGF, p-ERK, and Bcl-2 in brain tissues. In vitro, BMSC-HGF protected neurons against OGD-induced apoptosis. Inhibition of ERK phosphorylation abolished the neuroprotective effect of BMSCs-HGF against OGD. Conclusions BMSCs-HGF is a potential treatment for HIBD and that the ERK/Bcl-2 pathway is involved in the underlying neuroprotective mechanism.


Biologicals ◽  
2017 ◽  
Vol 45 ◽  
pp. 15-19 ◽  
Author(s):  
Kaveh Tari ◽  
Amir Atashi ◽  
Saied Kaviani ◽  
Mahshid AkhavanRahnama ◽  
Azadeh Anbarlou ◽  
...  

2020 ◽  
Vol 8 (A) ◽  
pp. 508-511
Author(s):  
Gusti Revilla ◽  
Henny Mulyani

BACKGROUND: Research on human bone marrow mesenchymal stem cells (hBM-MSCs) for burns healing has been known to increase the percentage of integrin expression of α2β1, type I collagen, transforming growth factor-β, and matrix metalloproteinases-9, but research on giving hBM-MSCs to growth factor expression in the process of re-epithelialization of burn healing has not been done. AIM: This study aims to the effect of hBM-MSCs given on the expression of epidermal growth factor (EGF) and EGF receptor (EGFR) in the process re-epithelialization in the healing of burn experimental rat. MATERIALS AND METHODS: This research is experimental with the post-test only control design, using 30 Wistar rats. Rats were divided into two groups, namely, control (phosphate-buffered saline), and the treatment was given hBM-MSCs, and stem cells were given subcutaneous doses of 2 × 106 cells/ml. Before being treated rats were anesthetized using xylazine and ketamine then the rats were burned in the dorsal (spine) with full-thickness. On the 3, 7, and 14 days, skin tissue was taken to see the expression of EGF and EGFR by immunohistochemical methods. This study was approved by the Ethics Commission of the Faculty of Medicine, Andalas University, Padang. The results of the study were analyzed by the t-test. RESULTS: Immunohistochemical examination of EGF and EGFR expressions after hBM-MSCs administration has significantly increased epithelialization compared with controls. Increased EGF expression was found on days 3 and 7 with moderate positive internal revenue service (IRS) assessment and on day 14 strong positive EGF expression, as well as EGFR expression on days 3 and 7 with moderate positive IRS assessment and on day 14 robust positive EGFR expression. CONCLUSION: This study concluded that giving of hBM-MSCs can increase the expression of EGF and EGFR which enhances the process of re-epithelialization thereby accelerating the healing of burns of experimental rats.


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