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開心術後患者に対する安全な早期離床の取り組みの成果と課題 -Outcomes of Early Mobilization for Open-Heart Surgery Patients-
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Proximalized total arch replacement can be safety performed by trainee （TraineeによるFrozen Elephant trunk法を用いた弓部大動脈置換術の安全性に関する検討）
Get PDFBackground The aim of the present study was to validate safety of total arch replacement (TAR) using a novel frozen elephant trunk device, operated by trainees as surgical education.
Methods Sixty-four patients including 19 patients (29.6%) with acute aortic dissection type A (AADA) underwent TAR in our institute between April 2014 and March 2019 were retrospectively analyzed. Twenty-nine patients were operated by trainees (group T) and 35 patients were operated by attending surgeons (group A).
Results Patient characteristics did not differ between groups. Operative time (409.4 ± 87.8 vs. 468.6 ± 129.6 minutes, p = 0.034), cardiopulmonary bypass time (177.7 ± 50.4 vs. 222.9 ± 596.7 minutes, p = 0.019), and hypothermic circulatory arrest time (39.5 ± 13.4 vs. 54.5 ± 18.5 minutes, p = 0.001) were significantly shorter in group A than in group T, but aortic clamping time did not differ between groups (115.3 ± 55.7 vs. 114.2 ± 35.0 minutes, p = 0.924) because the rate of concomitant surgery was higher in group A (37.1 vs. 10.3%, p = 0.014). Thirty-day mortality was 3.1% in the entire cohort. Although operation time was longer in group T, there were no significant difference in postoperative results between the groups, and the experience levels of the main operator were not independent predictors for in-hospital mortality + major postoperative complications. There was no difference in late death and aortic events between groups.
Conclusions The present study demonstrated that TAR can be safely performed by trainees, and suggests TAR as a possible and safe educational operation.博士（医学）旭川医科大
Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes （iPS細胞由来心筋細胞は、脂肪酸処理によって成熟心筋細胞様のエネルギー代謝へ変化する）
Get PDFHuman induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (iPSC-CMs) are a promising cell source for myocardial regeneration, disease modeling and drug assessment. However, iPSC-CMs exhibit immature fetal CM-like characteristics that are different from adult CMs in several aspects, including cellular structure and metabolism. As an example, glycolysis is a major energy source for immature CMs. As CMs mature, the mitochondrial oxidative capacity increases, with fatty acid β-oxidation becoming a key energy source to meet the heart's high energy demand. The immaturity of iPSC-CMs thereby limits their applications. The aim of this study was to investigate whether the energy substrate fatty acid-treated iPSC-CMs exhibit adult CM-like metabolic properties. After 20 days of differentiation from human iPSCs, iPSC-CMs were sequentially cultured with CM purification medium (lactate+/glucose-) for 7 days and maturation medium (fatty acids+/glucose-) for 3-7 days by mimicking the adult CM's preference of utilizing fatty acids as a major metabolic substrate. The purity and maturity of iPSC-CMs were characterized via the analysis of: (1) Expression of CM-specific markers (e.g., troponin T, and sodium and potassium channels) using RT-qPCR, Western blot or immunofluorescence staining and electron microscopy imaging; and (2) cell energy metabolic profiles using the XF96 Extracellular Flux Analyzer. iPSCs-CMs (98% purity) cultured in maturation medium exhibited enhanced elongation, increased mitochondrial numbers with more aligned Z-lines, and increased expression of matured CM-related genes, suggesting that fatty acid-contained medium promotes iPSC-CMs to undergo maturation. In addition, the oxygen consumption rate (OCR) linked to basal respiration, ATP production, and maximal respiration and spare respiratory capacity (representing mitochondrial function) was increased in matured iPSC-CMs. Mature iPSC-CMs also displayed a larger change in basal and maximum respirations due to the utilization of exogenous fatty acids (palmitate) compared with non-matured control iPSC-CMs. Etomoxir (a carnitine palmitoyltransferase 1 inhibitor) but not 2-deoxyglucose (an inhibitor of glycolysis) abolished the palmitate pretreatment-mediated OCR increases in mature iPSC-CMs. Collectively, our data demonstrate for the first time that fatty acid treatment promotes metabolic maturation of iPSC-CMs (as evidenced by enhanced mitochondrial oxidative function and strong capacity of utilizing fatty acids as energy source). These matured iPSC-CMs might be a promising human CM source for broad biomedical application.博士（医学）旭川医科大
Capillary-resident EphA7+ pericytes are multipotent cells with anti-ischemic effects through capillary formation （EphA7陽性毛細血管周細胞は多分化能を有し、血管形成能を介して、組織虚血を改善する）
Get PDFThe presence of pericytes (PCs) with multipotency and broad distribution along capillary suggests that microvasculature plays a role not only as a duct for blood fluid transport but also as a stem cell niche that contributes to tissue maintenance and regeneration. The lack of an appropriate marker for multipotent PCs still limits our understanding of their pathophysiological roles. We identified the novel marker EphA7 to detect multipotent PCs using microarray analysis of an immortalized PC library. PCs were isolated from microvessels of mouse subcutaneous adipose tissues, then EphA7+ PCs called capillary stem cells (CapSCs) were separated from EphA7- control PCs (ctPCs) using fluorescence-activated cell sorting system. CapSCs had highly multipotency that enabled them to differentiate into mesenchymal and neuronal lineages compared with ctPCs. CapSCs also differentiated into endothelial cells and PCs to form capillary-like structures by themselves. Transplantation of CapSCs into ischemic tissues significantly improved blood flow recovery in hind limb ischemia mouse model due to vascular formation compared with that of ctPCs and adipose stromal cells. These data demonstrate that EphA7 identifies a subpopulation of multipotent PCs that have high angiogenesis and regenerative potency and are an attractive target for regenerative therapies.博士（医学）旭川医科大