Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance

Kubo, Masayuki; Li, Tao‐Sheng; Suzuki, Ryo; Shirasawa, Bungo; Morikage, Noriyasu; Ohshima, Mako; Qin, Shu Lan; Hamano, Kimikazu

doi:10.1152/ajpheart.00856.2007

Cited by 48 publications

(57 citation statements)

References 35 publications

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“…Slides were then incubated with recombinant terminal deoxynucleotidyl transferase (GIBCO BRL, Life Technologies, Grand Island, NY, USA) and biotin 16-dUTP (Roche Diagnostics Corporation, Indianapolis, IN, USA) to label the nuclei of cells undergoing programmed cell death. 29 Colorimetric visualization, using avidin-HRP and DAB, was performed as described above.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Detergent-resistant microdomains mediate activation of host cell signaling in response to attaching–effacing bacteria

Shen–Tu

Schauer

Jones

et al. 2010

Laboratory Investigation

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Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes outbreaks of bloody diarrhea and the hemolytic-uremic syndrome. EHEC intimately adheres to epithelial cells, effaces microvilli and induces attaching-effacing (AE) lesions. Detergent-resistant microdomains (lipid rafts) serve as membrane platforms for the recruitment of signaling complexes to mediate host responses to infection. The aim of this study was to define the role of lipid rafts in activating signal transduction pathways in response to AE bacterial pathogens. Epithelial cell monolayers were infected with EHEC (MOI 100:1, 3 h, 371C) and lipid rafts isolated by buoyant density ultracentrifugation. Phosphoinositide 3-kinase (PI3K) localization to lipid rafts was confirmed using PI3K and anti-caveolin-1 antibodies. Mice with cholesterol storage disease Niemann-Pick, type C were used as in vivo models to confirm the role of lipid rafts in mediating signaling response to AE organisms. In contrast to uninfected cells, PI3K was recruited to lipid rafts in response to EHEC infection. Metabolically active bacteria and cells with intact cholesterol-rich microdomains were necessary for the recruitment of second messengers to lipid rafts. Recruitment of PI3K to lipid rafts was independent of the intimin (eaeA) gene, type III secretion system, and production of Shiga-like toxins. Colonization of NPC À/À colonic mucosa by Citrobacter rodentium and AE lesion formation were both delayed, compared with wild-type mice infected with the murine-specific AE bacterial pathogen. C. rodentium-infected NPC À/À mice had reduced colonic epithelial hyperplasia (64 ± 8.251 vs 112 ± 2.958 mm; Po0.05) and decreased secretion of IFN-g (17.6 ± 17.6 vs 71 ± 26.3 pg/ml, Po0.001). Lipid rafts mediate host cell signal transduction responses to AE bacterial infections both in vitro and in vivo. These findings advance the current understanding of microbial-eukaryotic cell interactions in response to enteric pathogens that hijack signaling responses mediated through lipid rafts.

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Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Detergent-resistant microdomains mediate activation of host cell signaling in response to attaching–effacing bacteria

Shen–Tu

Schauer

Jones

et al. 2010

Laboratory Investigation

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“…Similarly, the cytoprotective effect of HPC was demonstrated in a number of in vivo studies using clinically relevant ischaemic models (Table 2). In these studies, ex vivo HPC rendered stem and progenitor cells more resilient to cell death when transplanted into the infarcted myocardium (He et al, 2009;Hu et al, 2008;Tang et al, 2009;Uemura et al, 2006), ischaemic limb (Akita et al, 2003;Kubo et al, 2008;Li et al, 2002;Rosova et al, 2008) or ischaemic brain (Theus et al, 2008), and this finding was significantly correlated with improved functional recovery of the ischaemic tissues. For instance, transplantation of hypoxic preconditioned mesenchymal stem cells (MSCs) into the ischaemic myocardium showed enhanced therapeutic benefits in terms of infarct size reduction, increased angiogenesis, improved ventricular function and less adverse cardiac remodelling .…”

Section: Survivalmentioning

confidence: 99%

“…Mechanistic evaluations of the cytoprotective effect of HPC in stem and progenitor cells have implicated the up-regulation of a diverse array of soluble survival proteins such as growth factor VEGF (Akita et al, 2003;Potier et al, 2007), anti-apoptotic proteins Bcl-2 and Bcl-xL (Francis & Wei, 2010;Hu et al, 2008;Theus et al, 2008;Wang et al, 2008a), antioxidants heme oxygenase-1, hexokinase-2, catalase and superoxide dismutase (Kubo et Theus et al, 2008) and NO (Uemura et al, 2006;Ii et al, 2005) as the contributing factors. Other potential cytokines and growth factors that have been suggested are basic fibroblast growth factor (bFGF) (Gnecchi et al, 2006), hepatocyte growth factor (HGF) (Gnecchi et al, 2006), IL-1 (Kubo et al 2008), IL-6 (Hung et al, 2007a) and thymosin 4 (Gnecchi et al, 2006), though more supporting evidence for these factors in mediating the pro-survival effect of HPC in the context of stem cell preconditioning are warranted. In addition, HPC has also been shown to activate several transcription factors and signal transduction cascades that are known to be Table 2.…”

Section: Survivalmentioning

confidence: 99%

“…However, what remains unknown is whether these effects of HPC in promoting stem cell differentiation and in vivo engraftment can be translated when preconditioned stem cells are transplanted into adult tissues. To this end, early studies on peripheral blood mononuclear cells (Akita et al, 2003;Kubo et al, 2008) and MSCs (Leroux et al, 2010;Li et al, 2002) have indicated that HPC enhances not only their differentiation into endothelial progenitor cells (EPCs) in vitro but also promotes neovascularisation when transplanted into the ischaemic hindlimb. This effect was associated with improvement of blood perfusion and acceleration of tissue repair.…”

Section: Differentiation and Engraftmentmentioning

confidence: 99%

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Cytoprotection and Preconditioning for Stem Cell Therapy

Lim¹,

Dilley²,

Dusting³

2011

Advances in Regenerative Medicine

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“…To reduce invasiveness on collected transplanted cells, we used peripheral blood mononuclear cells (PBMNCs) instead of bone marrow cells and further examined the therapeutic effects of preconditioned PBMNCs on ischemic hindlimbs. Hypoxically pretreated PBMNCs improved microvessel density and limb blood flow in hindlimb ischemia models [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells

Mizoguchi

Ueno

Takeuchi

et al. 2018

Cell Physiol Biochem

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Background/Aims: We have developed a mixed-cell sheet consisting of autologous fibroblasts and peripheral blood mononuclear cells with a high potency for angiogenesis and wound healing against refractory cutaneous ulcers in mouse and rabbit models. To increase the effectiveness of the mixed sheet, we developed a multilayered mixed sheet. Methods: We assessed the therapeutic effects of multilayered sheets on cutaneous ulcers in mice. Growth factors and chemokines were assessed by enzyme-linked immunosorbent assay. Angiogenesis and fibroblast migration were measured by using tube formation and migration assays. Wound healing rate of cutaneous ulcers was evaluated in mice with diabetes mellitus. Results: The concentration of secreted vascular endothelial growth factor, hepatocyte growth factor, transforming growth factor, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in multilayered sheets was much higher than that in single-layered mixed-cell sheets (single-layered sheets) and multilayered sheets of fibroblasts alone (fibroblast sheets). The supernatant in multilayered sheets enhanced angiogenic potency and fibroblast migration compared with single-layered and fibroblast sheets in an in vitro experiment. The wound healing rate in the multilayered sheet-treated group was higher compared with the no-treatment group (control) at the early stage of healing. Moreover, both vessel lumen area and microvessel density in tissues treated with multilayered sheets were significantly increased compared with tissues in the control group. Conclusion: Multilayered sheets promoted wound healing and microvascular angiogenesis in the skin by supplying growth factors and cytokines. Accordingly, our data suggest that multilayered sheets may be a promising therapeutic material for refractory cutaneous ulcers.

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Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance

Abstract: Kubo M, Li TS, Suzuki R, Shirasawa B, Morikage N, Ohshima M, Qin SL, Hamano K. Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance.

Cited by 48 publications

References 35 publications

Detergent-resistant microdomains mediate activation of host cell signaling in response to attaching–effacing bacteria

Detergent-resistant microdomains mediate activation of host cell signaling in response to attaching–effacing bacteria

Cytoprotection and Preconditioning for Stem Cell Therapy

Treatment of Cutaneous Ulcers with Multilayered Mixed Sheets of Autologous Fibroblasts and Peripheral Blood Mononuclear Cells

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