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

Liu, Yang; Shen, Zhongyang; Wang, Raorao; Yin, Mingli; Zheng, Weiping; Wu, Bin; Liu, Tao; Song, Hongli

doi:10.3748/wjg.v23.i19.3449

Cited by 14 publications

(16 citation statements)

References 68 publications

(69 reference statements)

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“…Isolation, culture, and characterization of BMMSCs were performed according to previously described methods [24,27]. Briefly, BMMSCs were isolated from the femur and tibia of male SD rats and cultured in a cell culture incubator.…”

Section: Preparation and Identification Of Ho-1/bmmscsmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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Background: Donation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms. Methods: BMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated. Results: After liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased. Conclusions: HO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.

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Section: Preparation and Identification Of Ho-1/bmmscsmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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“…TGF-beta accelerates the formation of fibrous wraps and separates inflamed tissue from normal tissue, to reduce the formation of inflammatory granulation tissue, 70 while the increase of HO-1 can effectively inhibit the excessive action of osteoclasts. [71][72][73] Macrophages of the M1 and M2 phenotypes are indispensable in osteogenesis. Therefore, some scholars suggested that the key factor in determining macrophage-induced osteogenic or osteoclastic effects is the macrophage switch pattern rather than the specific macrophage phenotype.…”

Section: Pro-inflammatory and Pro-regenerative Gene Expression And Elmentioning

confidence: 99%

<p>Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages</p>

Chen¹,

You²,

Ma³

et al. 2020

IJN

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Purpose: Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO 2 nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated. Methods: TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO 2 nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated. Results: The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group. Conclusion: This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.

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“…Similarly, an in vitro study by Park and coworkers also revealed that a conditioned medium (CM) derived from fPMSCs could effectively reduce the expression of muscle atrophy-related proteins in myocytes, inhibit the production of ROS, and increase the expression of antioxidant enzymes. Mechanistically, recently studies have demonstrated that the nuclear factor erythroid-derived 2-like 2- (Nrf2-) Kelch-like ECH-associated protein 1- (keap1-) antioxidant response element (ARE) signaling pathway is one of the most important cellular defense mechanisms against oxidative stress [15, 16]. In this respect, MSCs modified with heme oxygenase-1 (HO-1) could enhance paracrine production of hepatocyte growth factor (HGF), interleukin- (IL-) 10, and the activity of Nrf2 to attenuate lipopolysaccharide- (LPS-) induced oxidative damage in pulmonary microvascular endothelial cells (PVECs) [16].…”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, recently studies have demonstrated that the nuclear factor erythroid-derived 2-like 2- (Nrf2-) Kelch-like ECH-associated protein 1- (keap1-) antioxidant response element (ARE) signaling pathway is one of the most important cellular defense mechanisms against oxidative stress [15, 16]. In this respect, MSCs modified with heme oxygenase-1 (HO-1) could enhance paracrine production of hepatocyte growth factor (HGF), interleukin- (IL-) 10, and the activity of Nrf2 to attenuate lipopolysaccharide- (LPS-) induced oxidative damage in pulmonary microvascular endothelial cells (PVECs) [16]. In addition, the marrow mesenchymal stem cell- (BMSC-) mediated alleviation of bleomycin-induced pulmonary fibrosis was found through a mechanism by activating the HO-1 expression and the Nrf2 pathway [15].…”

Section: Introductionmentioning

confidence: 99%

Nrf2/Keap1/ARE Signaling Mediated an Antioxidative Protection of Human Placental Mesenchymal Stem Cells of Fetal Origin in Alveolar Epithelial Cells

Yan

Jia

et al. 2019

Oxidative Medicine and Cellular Longevity

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The oxidative stresses are a major insult in pulmonary injury such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality. Mesenchymal stem cells (MSCs) hold a promise in treatments of many human diseases, mainly owing to their capacities of immunoregulation and antioxidative activity. The strong immunoregulatory role of human placental MSCs of fetal origin (hfPMSCs) has been previously demonstrated; their antioxidant activity, however, has yet been interrogated. In this report, we examined the antioxidative activity of hfPMSCs by accessing the ability to scavenge oxidants and radicals and to protect alveolar epithelial cells from antioxidative injury using both a cell coculture model and a conditioned culture medium (CM) of hfPMSCs. Results showed a comparable antioxidative capacity of the CM with 100 μM of vitamin C (VC) in terms of the total antioxidant capacity (T-AOC), scavenging abilities of free radicals DPPH, hydroxyl radical (·OH), and superoxide anion radical (O2-), as well as activities of antioxidant enzymes of SOD and GSH-PX. Importantly, both of the CM alone and cocultures of hfPMSCs displayed a protection of A549 alveolar epithelial cells from oxidative injury of 600 μM hydrogen peroxide (H2O2) exposure, as determined in monolayer and transwell coculture models, respectively. Mechanistically, hfPMSCs and their CM could significantly reduce the apoptotic cell fraction of alveolar epithelial A549 cells exposed to H2O2, accompanied with an increased expression of antiapoptotic proteins Bcl-2, Mcl-1, Nrf-2, and HO-1 and decreased proapoptotic proteins Bax, caspase 3, and Keap1, in comparison with naïve controls. Furthermore, hfPMSCs-CM (passage 3) collected from cultures exposed an inhibition of the Nrf2/Keap1/ARE signaling pathway which led to a significant reduction in caspase 3 expression in A549 cells, although the addition of Nrf2 inhibitor ML385 had no effect on the antioxidative activity of hfPMSCs-CM. These data clearly suggested that hfPMSCs protected the H2O2-induced cell oxidative injury at least in part by regulating the Nrf2-Keap1-ARE signaling-mediated cell apoptosis. Our study thus provided a new insight into the antioxidative mechanism and novel functions of hfPMSCs as antioxidants in disease treatments, which is warranted for further investigations.

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

Cited by 14 publications

References 68 publications

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

<p>Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages</p>

Nrf2/Keap1/ARE Signaling Mediated an Antioxidative Protection of Human Placental Mesenchymal Stem Cells of Fetal Origin in Alveolar Epithelial Cells

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