Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5‐azacytidine enhances therapeutic efficacy for myocardial infarction

Ling, Shukuan; Wang, Rui; Dai, Zhongquan; Nie, Jielin; Wang, Honghui; Tan, Yingjun; H, Cao; Huang, Zeng-Ming; Yue, Wan; Li, Yinghui

doi:10.1002/btpr.558

Cited by 21 publications

(17 citation statements)

References 44 publications

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“…There have been reports about the hormetic effects of chronic hypergravity in living organisms3456. Minois suggested that when D. melanogaster was exposed to 2 weeks of hypergravity (3 to 5G), it lived longer (in other words, hormetic effects on its longevity)17.…”

Section: Discussionmentioning

confidence: 99%

“…One of the most widely accepted model for simulating hypergravity is the centrifugal device. By using the centrifugal force due to the rotation, we could expose cultured cells or experimental animals to higher gravity than 1 G3456.…”

mentioning

confidence: 99%

“…Ling et al . suggested that when rat bone marrow mesenchymal stem cells were exposed to hypergravity and 5-azacytidine at the same time, their differentiation into cardiomyocytes was significantly improved4. Exposure to hypergravity could also upregulate expression of osteopontin in osteoblasts5, and enhance differentiation of neuronal cells6.…”

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confidence: 99%

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Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Jang

Jung

Kim

2016

Sci Rep

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We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

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Section: Discussionmentioning

confidence: 99%

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Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Jang

Jung

Kim

2016

Sci Rep

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“…In previous reports, several strategies have been investigated to enhance the therapeutic potential of MSCs, including (1) gene modification, that is, making MSCs overexpress cytokine genes or antiapoptotic genes, which significantly improved their therapeutic capacities or survival in ischemic tissues [21, 29]; (2) cotransplantation with adjuvant, such as adjuvant drugs or biomaterials, which may significantly enhance the retention or survival of transplanted cells [2, 26]; (3) preconditioning before transplantation with drugs, cytokines, or culture condition [30]. Gene modification is accompanied with risks to activate cancer genes and thus should be very cautious about in vivo application; cotransplantation with adjuvants is promising in future application; it could improve the ischemic microenvironment assisting the retention and survival of stem cells, but it fails to stimulate the therapeutic potentials of stem cells.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities

Zhang

Liu

Huo

et al. 2014

BioMed Research International

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Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels.

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“…10 Chang et al investigated altered gravity effects on human lung adenocarcinoma, demonstrating the ability of simulated microgravity to decrease the metastatic potential of this tumor cell line. 11 Other researchers used microgravity stimulation as an approach for the development of a large amount of β-cell spheroids, which once transplanted in mice are able to improve the symptoms of diabetes.…”

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Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts

Rocca¹,

Marino²,

Rocca³

et al. 2015

IJN

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Background Enhancement of the osteogenic potential of mesenchymal stem cells (MSCs) is highly desirable in the field of bone regeneration. This paper proposes a new approach for the improvement of osteogenesis combining hypergravity with osteoinductive nanoparticles (NPs). Materials and methods In this study, we aimed to investigate the combined effects of hypergravity and barium titanate NPs (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity effects on NP internalization. To obtain the hypergravity condition, we used a large-diameter centrifuge in the presence of a BTNP-doped culture medium. We analyzed cell morphology and NP internalization with immunofluorescent staining and coherent anti-Stokes Raman scattering, respectively. Moreover, cell differentiation was evaluated both at the gene level with quantitative real-time reverse-transcription polymerase chain reaction and at the protein level with Western blotting. Results Following a 20 g treatment, we found alterations in cytoskeleton conformation, cellular shape and morphology, as well as a significant increment of expression of osteoblastic markers both at the gene and protein levels, jointly pointing to a substantial increment of NP uptake. Taken together, our findings suggest a synergistic effect of hypergravity and BTNPs in the enhancement of the osteogenic differentiation of MSCs. Conclusion The obtained results could become useful in the design of new approaches in bone-tissue engineering, as well as for in vitro drug-delivery strategies where an increment of nanocarrier internalization could result in a higher drug uptake by cell and/or tissue constructs.

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Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5‐azacytidine enhances therapeutic efficacy for myocardial infarction

Abstract: The biological ex vivo cardiomyogenic differentiation of adult BMSCs with hypergravity and 5-Aza prior to their transplantation is feasible and appears to improve their in vivo cardiac differentiation as well as the functional recovery in a rat model of the infarcted myocardium.

Cited by 21 publications

References 44 publications

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities

Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts

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