scholarly journals Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

2017 ◽  
Vol 23 (19) ◽  
pp. 3449 ◽  
Author(s):  
Liu Yang ◽  
Zhong-Yang Shen ◽  
Rao-Rao Wang ◽  
Ming-Li Yin ◽  
Wei-Ping Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Energy Metabolism ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Wu ◽  
Hong-Li Song ◽  
Yang Yang ◽  
Ming-Li Yin ◽  
Bo-Ya Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
The Other ◽  
Heme Oxygenase 1 ◽  
Immunomodulatory Effects ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-βlevels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γlevels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.

Impact of anti-apoptotic and anti-oxidative effects of bone marrow mesenchymal stem cells with transient overexpression of heme oxygenase-1 on myocardial ischemia

2010 ◽  
Vol 298 (5) ◽  
pp. H1320-H1329 ◽  
Author(s):  
Toshinari Tsubokawa ◽  
Kunimasa Yagi ◽  
Chiaki Nakanishi ◽  
Masahiko Zuka ◽  
Atsushi Nohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Myocardial Injury ◽  
Tissue Injury ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Infarction Size ◽  
The Impact

Although mesenchymal stem cells (MSCs) have therapeutic potential for tissue injury, intolerance and poor cell viability limit their reparative capability. Therefore, we examined the impact of bone marrow-derived MSCs, in which heme oxygenase-1 (HO-1) was transiently overexpressed, on the repair of an ischemic myocardial injury. When MSCs and HO-1-overexpressed MSCs (MSCHO-1) were exposed to serum deprivation/hypoxia or H2O2-induced oxidative stress, MSCHO-1 exhibited increased resistance to cell apoptosis compared with MSCs (17 ± 1 vs. 30 ± 2%, P < 0.05) and were markedly resistant to cell death (2 ± 1 vs. 32 ± 2%, P < 0.05). Under these conditions, vascular endothelial growth factor (VEGF) production was 2.1-fold greater in MSCHO-1 than in MSCs. Pretreatment of MSCs and MSCHO-1 with phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (Akt) pathway inhibitors such as LY-294002 (50 μM) or wortmannin (100 nM) significantly decreased VEGF production. In a rat infarction model with MSCs or MSCHO-1 (5 × 106 ± 0.1 × 106 cells/rat) transplantation, the number of TdT-mediated dUTP nick end-labeling-positive cells was significantly lower in the MSCHO-1 group than in the MSC group (12.1 ± 1.0 cells/field vs. 26.5 ± 2.6, P < 0.05) on the 4th day after cell transplantation. On the 28th day, increased capillary density associated with decreased infarction size was observed in the MSCHO-1 group (1,415 ± 47/mm2 with 21.6 ± 2.3%) compared with those in the MSCs group (1,215 ± 43/mm2 with 28.2 ± 2.3%, P < 0.05), although infarction size relative to area at risk was not different in each group at 24 h after transplantation. These results demonstrate that MSCHO-1 exhibit markedly enhanced anti-apoptotic and anti-oxidative capabilities compared with MSCs, thus contributing to improved repair of ischemic myocardial injury through cell survival and VEGF production associated with the PI 3-kinase/Akt pathway.

Sign in / Sign up

Export Citation Format

Share Document