Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Hepatic Ischemia Reperfusion Injury in a Rat Model

BACKGROUND: Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy. METHODOLOGY/PRINCIPAL FINDINGS: We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration

モモセン コウサイキン ビョウキン(オモ ニXanthomonas arboricola pv. pruni)ノ ヤクザイ カンジュセイ ニ カンスル ケンキュウ

モモせん孔細菌病は重要病害の一つであり,国内ではXanthomonas arboricola pv. pruni, Pseudomonas syringae pv. syringae およびBrenneria nigrifluensの3種が病原細菌として報告されている。一般的に本病の主病原はX. a. pv. pruniであるとされているが,それを詳細に調査した報告は少ない。また,本病の防除は抗生物質剤を中心とした薬剤の散布が主である。抗生物質剤は様々な病害で薬剤耐性菌の発生が報告されており問題となっている。本病においても耐性菌の出現による防除効果の低下が懸念されている。そこで,2008年から2011年の4年間に合計7県151ほ場からモモせん孔細菌病罹病試料を採取し,病原細菌を分離,国内で発生している本病の主病原を再確認したところ,分離した菌株のほとんどがX. a. pv. pruniであったことから本病の主病原はX. a. pv. pruniである可能性が示唆された。さらに,菌株のオキシテトラサイクリン,オキソリニック酸およびストレプトマイシンに対する最小生育阻止濃度(MIC)を調査したところ,オキシテトラサイクリンおよびオキソリニック酸に対するMICは25ppm以下であった。一方,ストレプトマイシンに対してはMICが2000ppm以上を示す菌株が200菌株と全体の43%を占めており,ストレプトマイシンに対して耐性を有するX. a. pv. pruniが比較的高い割合で存在することが示唆された。Although bacterial shot hole disease is one of the most important diseases in peach production and three pathogens have been reported from the disease in Japan, there is little investigation on the dominant pathogen. As the use of bactericidal antibiotics is indispensable to control this disease, emergence of the causal bacteria with resistance to bactericides has been reported and is noticed as a serious problem in peach production. Samples of peach plants with bacterial shot hole disease were collected from 151 fields in 7 prefectures in four years from 2008 to 2011 for isolation and reaffirmation of the main causal bacteria. Most frequently isolated bacteria was identified as Xanthomonas arboricola pv. pruni, recognized as the dominant causal agent of bacterial shot hole disease of peach. The bacterial isolates identified as the dominant pathogen were examined for their minimal inhibitory concentration (MIC) against oxytetracycline, oxolinic acid and streptomycin to evaluate their susceptibility. Although all isolates tested were susceptible to oxytetracycline and oxolinic acid and showed <25ppm (MIC), 200 isolates (43% of tested isolates) showed more than 2000ppm (MIC) to streptomycin and were judged as resistant. The results of the survey showed the considerably higher population of X. a. pv. pruni with resistance to streptomycin in peach fields

Impact of catheter-induced iatrogenic coronary artery dissection with or without postprocedural flow impairment: A report from a Japanese multicenter percutaneous coronary intervention registry.

Despite the ever-increasing complexity of percutaneous coronary intervention (PCI), the incidence, predictors, and in-hospital outcomes of catheter-induced coronary artery dissection (CICAD) is not well defined. In addition, there are little data on whether persistent coronary flow impairment after CICAD will affect clinical outcomes. We evaluated 17,225 patients from 15 participating hospitals within the Japanese PCI registry from January 2008 to March 2016. Associations between CICAD and in-hospital adverse cardiovascular events were evaluated using multivariate logistic regression. Outcomes of patients with CICAD with or without postprocedural flow impairment (TIMI flow ≤ 2 or 3, respectively) were analyzed. The population was predominantly male (79.4%; mean age, 68.2 ± 11.0 years); 35.6% underwent PCI for complex lesions (eg. chronic total occlusion or a bifurcation lesion.). CICAD occurred in 185 (1.1%), and its incidence gradually decreased (p < 0.001 for trend); postprocedural flow impairment was observed in 43 (23.2%). Female sex, complex PCI, and target lesion in proximal vessel were independent predictors (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.53-3.10; OR, 2.19; 95% CI, 1.58-3.04; and OR, 1.55; 95% CI, 1.06-2.28, respectively). CICAD was associated with an increased risk of in-hospital adverse events (composite of new-onset cardiogenic shock and new-onset heart failure) regardless of postprocedural flow impairment (OR, 10.9; 95% CI, 5.30-22.6 and OR, 2.27; 95% CI, 1.20-4.27, respectively for flow-impaired and flow-recovered CICAD). In conclusion, CICAD occurred in roughly 1% of PCI cases; female sex, complex PCI, and proximal lesion were its independent risk factors. CICAD was associated with adverse in-hospital cardiovascular events regardless of final flow status. Our data implied that the appropriate selection of PCI was necessary for women with complex lesions

Decrease of luciferase activity.

<p>The expression level of luciferase was postoperatively observed using a noninvasive living image acquisition IVIS system. Accumulation of MSCs in the remnant liver. <b>A</b>. Most of the MSCs became trapped in the remnant liver. Thereafter, the luciferase activity diminished with time. <b>B</b>. The largest level of luciferase was 187272±119507 photons/sec/cm²/sr (sr = units of solid angle or steradian). (24 h vs. 168 h: <i>P</i><0.03; 24 h vs. 120 h: P<0.05; 72 h vs. 168 h: P<0.05).</p

Remnant liver volume changes.

<p>The liver regeneration rate is expressed as remnant liver weight/estimated whole liver weight.</p

Histopathological changes and Suzuki Score.

<p>Hematoxylin eosin staining of I/R-injured liver sections from the MSC group (<b>A</b>. left panel) and the Control group (<b>B</b>. right panel). <b>C</b>. The lower levels of congestion, vacuolization, and necrosis were seen in the MSC group. Suzuki scores = (MSC group vs. Control group: 1.4±1.3 vs. 3.9±1.7, <i>p</i><0.03).</p

A new rat model of major hepatectomy with I/R injury.

<p>A new rat model of major hepatectomy with I/R injury.</p

Minimal TUNEL-positive hepatocytes by BM-MSC transplantation.

<p>TUNEL staining of I/R-injured liver sections from the MSC group (<b>A</b>. upper panel) and the Control group (<b>B</b>. lower panel). <b>C</b>. Quantification of TUNEL-positive hepatocyte nuclei was assessed by calculating the mean of the number of TUNEL-positive hepatocytes in 10 random high-power fields per animal. Abbreviations: CV, central vein; PV, portal vein.</p

Characterization of BM-MSCs by expression of CD29⁺, CD31⁻, CD34⁻, and CD105⁺.

<p><b>A</b>. Bright-field image. <b>B–C</b>. CD29 and CD105 surface antigens are positive. <b>D</b>. CD31 surfice antigen is negative, <b>E</b>. CD34 surfice antigen negative.</p