Background: Saphenous vein grafts (SVGs) are broadly used in coronary artery bypass grafting despite their inferior patency compared with arterial grafts. Recently, the no‐touch technique (NT), in which an SVG is harvested with a pedicle of perivascular adipose tissue (PVAT) without conduit distension, was shown to improve long‐term patency compared with conventional preparation (CV), wherein outer tissue is removed with distension. The NT was also reportedly associated with reduced atherosclerosis. Although endothelial damage provoked by conventional distension may underlie poor patency when CV is performed, the precise mechanisms underlying the salutary effects of the NT have been unclear. Methods and Results: Residual SVGs prepared with CV (CV‐SVGs) or NT (NT‐SVGs) were obtained during coronary artery bypass grafting. Nitric oxide (NO ₂ ⁻ /NO ₃ ⁻ (NO _x )) levels after 24 hours of tissue culture were quantified. The protein expression and localization were analyzed. The isometric force of SVG strips was measured. NT‐SVGs showed superior NO _x production to CV‐SVGs. PVAT generated the majority of NO _x in NT‐SVGs. PVAT highly expressed arginosuccinate synthase 1, a rate‐limiting enzyme in the molecular circuit for NO synthesis, thereby continuously providing the substrate for NO. A substantial level of endothelial NO synthase was also expressed in PVAT. Pharmacological inhibition of arginosuccinate synthase 1 or endothelial NO synthase significantly suppressed the NO _x production in NT‐SVGs. PVAT induced vasorelaxation through NO production, even in the endothelium‐denuded SVG strips. Conclusions: Preserving PVAT was predominantly involved in the superior NO _x production in NT‐SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT‐SVGs.

Type II endoleak (T2EL) is the most common type of endoleak after endovascular aneurysm repair (EVAR) and a common indication for reintervention due to late sac enlargement. Although pre-emptive embolization of the inferior mesenteric artery (IMA) has been proposed to prevent this, no studies have prospectively demonstrated its efficacy. This study aimed to prove the validity of IMA embolization during EVAR in selective cases by analyzing the mid-term outcomes of a randomized clinical trial (RCT). This single-center, parallel-group, non-blinded RCT included participants at high risk of T2EL, characterized by a patent IMA in conjunction with one or more following risk factors: a patent IMA ≥3 mm in diameter, lumbar arteries ≥2 mm in diameter, or an aortoiliac-type aneurysm. The participants were randomly assigned to two groups in a 1:1 ratio: one undergoing EVAR with IMA embolization and the other without. The primary endpoint was T2EL occurrence. The secondary endpoints included aneurysm sac changes and reintervention. In addition to RCT participants, outcomes of patients with low risk of T2EL were also analyzed. The embolization and non-embolization groups each contained 53 patients. Five-year follow-up after the last patient enrollment revealed that T2ELs occurred in 28.3% and 54.7% of patients in the IMA embolization and non-embolization groups, respectively (P = .006). Both freedom from T2EL-related sac enlargement ≥5 mm and cumulative incidence of sac shrinkage ≥5 mm were significantly higher in the IMA embolization group than in the non-embolization group (95.5% vs 73.6% at 5 years; P = .021; 54.2% vs 33.6% at 5 years; P = .039, respectively). The freedom from T2EL-related sac enlargement ≥10 mm, an alternative indicator for T2EL-related reintervention, showed similar results (100% vs 90.4% at 5 years; P = .019). Outcomes in the low-risk group were preferable than those in the non-embolization group and comparable to those in the IMA embolization group. A lower threshold for pre-emptive IMA embolization when implementing EVAR would be more appropriate if limited to patients at high risk of T2ELs.

Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and nonischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and nonischemic heart failure was induced by an IP injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2 × 105 c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p < 0.05 vs. control therapy). In the nonischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p < 0.05 vs. control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of nonischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.

To explore the impact of the no-touch harvesting technique on the vessel diameter of saphenous vein grafts. This retrospective, single-center study enrolled 166 patients who underwent isolated coronary artery bypass grafting using saphenous vein grafts. Saphenous vein grafts were harvested conventionally in 83 patients (conventional group) and using the no-touch technique in 83 patients (no-touch group). We analyzed graft patency and the vessel diameters of saphenous vein grafts in the pre- and postoperative states. The diameter mismatch between the saphenous vein grafts and the coronary artery at the anastomotic site was also measured; preoperative diameter was measured using ultrasound imaging, and the postoperative diameter was measured using electrocardiogram-gated enhanced computed tomography. A total of 135 saphenous vein grafts (66 and 69 grafts in the conventional and no-touch groups, respectively) were evaluated for postoperative patency. Graft patency was equivalent in the 2 groups (conventional, 96.9% vs no-touch, 100%; P = .24). A detailed evaluation was performed in 109 saphenous vein grafts (52 and 57 grafts in the conventional and no-touch groups, respectively). Saphenous vein graft diameter was significantly distended in the conventional group (preoperative, 2.6 ± 0.7 mm vs postoperative, 3.4 ± 0.5 mm; P < .0001). However, saphenous vein graft diameter did not change in the no-touch group (preoperative, 2.9 ± 0.4 mm vs postoperative 2.8 ± 0.4 mm, P = .33). The diameter mismatch was significantly smaller in the no-touch group (conventional 1.4 ± 0.6 mm vs no-touch 1.0 ± 0.4 mm, P < .0001). The no-touch technique avoids the expansion of graft diameter and diameter mismatch between the saphenous vein grafts and coronary artery.

In our previous study, we found that dry-preserved multilayered fibroblast cell sheets promoted angiogenesis and wound healing in a mouse ulcer model by releasing high levels of intracellular fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF), from dried cells. In the present study, to identify which cell types are suitable for human dry-preserved cell sheets (dry sheets), we compared the intracellular FGF2 levels in seven types of cells reported as cell sheets for clinical use or preclinical studies. FGF2 levels were high in mesenchymal cells, including human oral fibroblasts (HOFs) and human dermal fibroblasts (HDFs), human dental pulp stem cells (DPSCs), and human mesenchymal stem cells (MSCs); in contrast, FGF2 levels in human umbilical vascular endothelial cells (HUVECs), human skeletal muscle myoblasts (SkMMs), and human epidermal keratinocytes (HEKs) were remarkably low, approximately 25% those in fibroblasts. In addition, we prepared dry sheets from HOFs, DPSCs, and MSCs, and analyzed the growth factors released from each dry sheet upon rehydration. High levels of FGF2, HGF, and VEGF were detected in the eluate prepared by immersing each dry sheet. In particular, FGF2 and HGF were the most abundant in HOFs. An in vitro cell proliferation assay showed that these eluates significantly enhanced HUVEC proliferation compared to control cells. Furthermore, cells incubated with HOF eluate showed significantly higher cell proliferation than cells incubated with DPSC and MSC eluates. However, this proliferative response was significantly blocked by FGF2-neutralizing antibodies. These results demonstrate that growth factors released from human dry sheets have physiological activity and that this activity is mainly mediated by the effect of FGF2. Fibroblasts are ideal for the clinical application of dry-preserved cell sheets in humans owing to their high intracellular FGF2 content, fast cell proliferation, ease of handling, availability, and low culture costs, making them the most suitable cell source for regenerative medicine, with FGF2 release as the mechanism of action.