Glomerular Endothelial Cell Receptor ADGRF5 and the Integrity of the Glomerular Filtration Barrier.

BACKGROUND: Glomerular endothelial cells are recognized to be important for maintaining the glomerular filtration barrier. ADGRF5, an adhesion G protein-coupled receptor, has been suggested to be involved in endothelial cell function. However, the role of ADGRF5 in the glomerular filtration barrier integrity remains elusive. METHODS: Cellular expression of ADGRF5 in mouse glomerulus was determined by histological analyses. The impact of ADGRF5 deletion on the glomerular morphology, kidney function, and glomerular endothelial gene/protein expression was then analyzed using ADGRF5 knockout (Adgrf5-/-) mice and human primary glomerular endothelial cells. RESULTS: ADGRF5 was specifically expressed in the capillary endothelial cells within the glomerulus. Adgrf5-/- mice developed albuminuria and impaired kidney function with morphological defects in the glomeruli, namely glomerular hypertrophy, glomerular basement membrane splitting and thickening, diaphragmed fenestration and detachment of the glomerular endothelial cells, and mesangial interposition. These defects were accompanied by the altered expression of genes responsible for glomerular basement membrane organization (type IV collagens and laminins) and Krüppel-like factor 2 (Klf2) in glomerular endothelial cells. Moreover, ADGRF5 knockdown decreased COL4A3 and COL4A4 expression and increased KLF2 expression in human primary glomerular endothelial cells. CONCLUSIONS: The loss of ADGRF5 resulted in altered gene expression in glomerular endothelial cells, and perturbed the structure and permselectivity of the glomerular filtration barrier.

Configuration of the neoaortic root after chimney reconstruction in the Norwood procedure.

OBJECTIVES: After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. METHODS: Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5-6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. RESULTS: The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. CONCLUSIONS: Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.

Roles of the mechanosensitive ion channel Piezo1 in the renal podocyte injury of experimental hypertensive nephropathy.

Glomerular podocyte injury plays an essential role in proteinuria pathogenesis, a hallmark of chronic kidney disease, including hypertensive nephropathy. Although podocytes are susceptible to mechanical stimuli, their mechanotransduction pathways remain elusive. Piezo proteins, including Piezo1 and 2, are mechanosensing ion channels that mediate various biological phenomena. Although renal Piezo2 expression and its alteration in rodent dehydration and hypertension models have been reported, the role of Piezo1 in hypertensive nephropathy and podocyte injury is unclear. In this study, we examined Piezo1 expression and localization in the kidneys of control mice and in those of mice with hypertensive nephrosclerosis. Uninephrectomized, aldosterone-infused, salt-loaded mice developed hypertension, albuminuria, podocyte injury, and glomerulosclerosis. RNAscope in situ hybridization revealed that Piezo1 expression was enhanced in the podocytes, mesangial cells, and distal tubular cells of these mice compared to those of the uninephrectomized, vehicle-infused control group. Piezo1 upregulation in the glomeruli was accompanied by the induction of podocyte injury-related markers, plasminogen activator inhibitor-1 and serum/glucocorticoid regulated kinase 1. These changes were reversed by antihypertensive drug. Exposure of Piezo1-expressing cultured podocytes to mechanical stretch activated Rac1 and upregulated the above-mentioned markers, which was antagonized by the Piezo1 blocker grammostola mechanotoxin #4 (GsMTx4). Administration of Piezo1-specific agonist Yoda1 mimicked the effects of mechanical stretch, which was minimized by the Yoda1-specific inhibitor Dooku1 and Rac inhibitor. Rac1 was also activated in the above-mentioned hypertensive mice, and Rac inhibitor downregulated gene expression of podocyte injury-related markers in vivo. Our results suggest that Piezo1 plays a role in mechanical stress-induced podocyte injury.

A new predictor of the optimal pulmonary artery reconstruction method during the arterial switch operation.

OBJECTIVES: The aim of this study was to more accurately predict the optimal pulmonary artery (PA) reconstruction procedure (Lecompte manoeuvre or original Jatene procedure) during the arterial switch operation, we focused on the horizontal sectioning (HS) angle between the left hilum PA and the great arteries using preoperative computed tomography imaging. METHODS: We defined the HS angle α (ß) as the angle between the tangential line from the posterior (anterior) wall of the left PA at the hilum to the left anterior (right posterior) surface of the main PA and the tangential line from the left surface of the ascending aorta to the left anterior (right posterior) surface of the main PA. We identified 14 consecutive patients diagnosed with transposition of the great arteries or transposition of the great artery-type double-outlet right ventricle who underwent preoperative computed tomography imaging. The original Jatene or Lecompte procedure was used for 9 (OJ group) and 5 (L group) patients. Relationships of the great arteries of the OJ and L groups were side by side in 8 and 2 patients, oblique in 1 and 1 patient and anteroposterior in 0 and 2 patients, respectively. RESULTS: In the OJ group, ß was greater than α in all patients. The median α/ß value was 0.618. In group L, α was greater than ß in all patients. The median α/ß was 1.307. Left PA stenosis caused by stretching was not observed in the L group. Coronary obstruction was not identified in the OJ group. Left PA stenosis behind the neo-ascending aorta was observed in 1 patient in the OJ group and required reoperation. CONCLUSIONS: The HS angle may be a useful predictor of optimal intraoperative PA reconstruction during arterial switch operation, especially for side-by-side or oblique relationships.

Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone.

The recent discovery of mechanosensitive ion channels has promoted mechanobiological research in the field of hypertension and nephrology. We previously reported Piezo2 expression in mouse mesangial and juxtaglomerular renin-producing cells, and its modulation by dehydration. This study aimed to investigate how Piezo2 expression is altered in hypertensive nephropathy. The effects of the nonsteroidal mineralocorticoid receptor blocker, esaxerenone, were also analyzed. Four-week-old Dahl salt-sensitive rats were randomly assigned to three groups: rats fed a 0.3% NaCl diet (DSN), rats fed a high 8% NaCl diet (DSH), and rats fed a high salt diet supplemented with esaxerenone (DSH + E). After six weeks, DSH rats developed hypertension, albuminuria, glomerular and vascular injuries, and perivascular fibrosis. Esaxerenone effectively decreased blood pressure and ameliorated renal damage. In DSN rats, Piezo2 was expressed in Pdgfrb-positive mesangial and Ren1-positive cells. Piezo2 expression in these cells was enhanced in DSH rats. Moreover, Piezo2-positive cells accumulated in the adventitial layer of intrarenal small arteries and arterioles in DSH rats. These cells were positive for Pdgfrb, Col1a1, and Col3a1, but negative for Acta2 (αSMA), indicating that they were perivascular mesenchymal cells different from myofibroblasts. Piezo2 upregulation was reversed by esaxerenone treatment. Furthermore, Piezo2 inhibition by siRNA in the cultured mesangial cells resulted in upregulation of Tgfb1 expression. Cyclic stretch also upregulated Tgfb1 in both transfections of control siRNA and Piezo2 siRNA. Our findings suggest that Piezo2 may have a contributory role in modulating the pathogenesis of hypertensive nephrosclerosis and have also highlighted the therapeutic effects of esaxerenone on salt-induced hypertensive nephropathy. Mechanochannel Piezo2 is known to be expressed in the mouse mesangial cells and juxtaglomerular renin-producing cells, and this was confirmed in normotensive Dahl-S rats. In salt-induced hypertensive Dahl-S rats, Piezo2 upregulation was observed in the mesangial cells, renin cells, and notably, perivascular mesenchymal cells, suggesting its involvement in kidney fibrosis.

Multiple Pulmonary Artery Plasty With Tissue-Engineered Vascular Grafts.

In pediatric cardiovascular surgery, the autologous pericardium is useful for pulmonary artery augmentation. However, in some cases, the autologous pericardium may not be available for various reasons. Since 2014, we have developed tissue-engineered vascular grafts (TEVGs) and obtained good results. We report a successful case of multiple pulmonary artery plasty with TEVGs for pulmonary atresia/ventricular septal defect with major aortopulmonary collateral arteries. TEVGs are useful alternatives to autologous pericardium in pediatric cardiovascular operations that often require multistage procedures.

Surgical repair of a posterior left ventricular aneurysm in a 4-year-old boy.

Left ventricular aneurysms are rarely encountered in pediatric patients. A 4-year-old boy was diagnosed with severe mitral regurgitation and a posterior left ventricular aneurysm associated with a viral infection. The aneurysm was surgically resected and plicated longitudinally with a combination of an interrupted mattress and continuous over-and-over sutures with an outer felt reinforcement. The mitral regurgitation was reduced to a trivial degree postoperatively. The patient's postoperative recovery was good. He was discharged 31 days after surgery without cardiac dysfunction or lethal arrhythmia. Considering the location and spread of the aneurysm, an appropriate surgical procedure should be adopted for pediatric patients.

Formalin-free soft embalming of human cadavers using N-vinyl-2-pyrrolidone: perspectives for cadaver surgical training and medical device development.

The traditional apprenticeship approach to surgical skill education for young surgeons has drastically changed to more systematic surgical training using cadavers. Cadavers fixed with formalin are not suitable for surgical training because of their associated health hazards and overhardening. Recently, we established a formalin-free soft preservation method for human cadavers using N-vinyl-2-pyrrolidone. Since 2012, 61 cadavers have been embalmed with pyrrolidone in our institution. Tissues of pyrrolidone-embalmed cadavers are soft and pliable, and their bodies can be preserved for as long as 37 months without any signs of corruption. In this review, we introduce our recent attempts to apply pyrrolidone-embalmed cadavers in surgical and medical procedure training, including endotracheal intubation, motion physiology of the vocal folds, laparoscopic surgery, endoscopic skull base surgery, and development of novel medical devices. Future research perspectives on pyrrolidone embalming are discussed.

Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells.

The kidney plays a central role in body fluid homeostasis. Cells in the glomeruli and juxtaglomerular apparatus sense mechanical forces and modulate glomerular filtration and renin release. However, details of mechanosensory systems in these cells are unclear. Piezo2 is a recently identified mechanically activated ion channel found in various tissues, especially sensory neurons. Herein, we examined Piezo2 expression and regulation in mouse kidneys. RNAscope in situ hybridization revealed that Piezo2 expression was highly localized in mesangial cells and juxtaglomerular renin-producing cells. Immunofluorescence assays detected GFP signals in mesangial cells and juxtaglomerular renin-producing cells of Piezo2GFP reporter mice. Piezo2 transcripts were observed in the Foxd1-positive stromal progenitor cells of the metanephric mesenchyme in the developing mouse kidney, which are precursors of mesangial cells and renin-producing cells. In a mouse model of dehydration, Piezo2 expression was downregulated in mesangial cells and upregulated in juxtaglomerular renin-producing cells, along with the overproduction of renin and enlargement of the area of renin-producing cells. Furthermore, the expression of the renin coding gene Ren1 was reduced by Piezo2 knockdown in cultured juxtaglomerular As4.1 cells under static and stretched conditions. These data suggest pivotal roles for Piezo2 in the regulation of glomerular filtration and body fluid balance.

Effects of leg compression and calf muscle contraction by active ankle motion on venous hemodynamics in sitting individuals.

OBJECTIVES: To clarify the effects of compression and active ankle motion on venous hemodynamics in healthy sitting individuals. METHODS: In the sitting position, 14 participants performed plantar flexion and dorsiflexion of the ankle for 3 s each without compression. Changes in the calf volume were recorded using air plethysmography. Subsequently, the process was repeated with the application of tubular elastic bandage (TEB), followed by anti-thrombotic stocking (ATS). RESULTS: The median interface pressure at the calf was 16 mmHg with TEB and 21 mmHg with ATS. Without compression (N), the median venous volume was 76 mL. This was reduced to 58 mL with TEB and 56 mL with ATS (p < .01 vs. N for both). On the other hand, ejection volume by plantar flexion in N (27 mL) was not significantly changed with TEB (31 mL) or ATS (31 mL). Also, ejection volume by dorsiflexion in N (53 mL, p < .001 vs. plantar flexion) was not significantly changed with TEB (53 mL, p < .01 vs. plantar flexion) or ATS (41 mL, p < .05 vs. plantar flexion). CONCLUSIONS: The venous volume, which is defined as the change in enclosed calf volume from elevation to dependency, in the sitting position reduced similarly with TEB and ATS; however, the ejection volumes did not change significantly. Dorsiflexion exerted a larger ejection volume than plantar flexion in the sitting position.

Perivascular Adipose Tissue Is a Major Source of Nitric Oxide in Saphenous Vein Grafts Harvested via the No-Touch Technique.

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 (NO2-/NO3- (NOx)) 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 NOx production to CV-SVGs. PVAT generated the majority of NOx 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 NOx 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 NOx production in NT-SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT-SVGs.

Hardness Sensed by Skin Palpation in Legs with Lymphedema Is Predominantly Correlated with Dermal Thickening.

Background: We aimed to clarify whether pathological changes in skin and subcutaneous tissue with lymphedema affected the skin hardness sensed by palpation. Methods and Results: In 50 patients with unilateral legs with lymphedema (LE), the skin hardness of the lower inner thigh and lower inner calf was determined using a scale ranging from 1 (softest) to 7 (hardest) based on palpation. Then, the skin hardness was correlated with the measurements of skin/subcutaneous tissue ultrasonography images obtained from the palpated parts. Multivariate logistic regression analysis demonstrated that dermal thickness was a significant factor that affected the difference in skin hardness between the LE and the contralateral asymptomatic leg for both thigh (p < 0.05) and calf (p < 0.01). When the thigh and calf in the LE were individually studied, subcutaneous echogenicity (p < 0.05), indicating subcutaneous inflammation/fibrosis, and subcutaneous thickness (p < 0.01) also seemed to affect skin hardness, respectively. Conclusions: The skin hardness sensed in the LE seemed to be affected predominantly by dermal thickening. In addition, the pathological changes in the subcutaneous tissue caused by LE seemed to have an impact on skin hardness. Clinical Trial Registration number 2020-150.

A case of redo tricuspid valve repair after neonatal cone operation for Ebstein's anomaly.

Cone reconstruction for Ebstein's anomaly, although effective, is challenging in neonatal cases. Very few reports have discussed recurrent regurgitation. Herein, we report a successful redo tricuspid valve repair for recurrent regurgitation 5 years after cone reconstruction. A 5-year-old boy underwent cone reconstruction for Ebstein's anomaly in the neonatal period. Although tricuspid regurgitation reduced initially, it subsequently worsened. The mechanisms of regurgitation are dilatation of the anteroseptal commissure, indentation in the septal leaflet, and foreshortening of the anterior leaflet. Augmentation of the anterior leaflet using an elliptic autologous pericardium and mending of the gaping commissure and indentation markedly reduced the regurgitation.

A pilot study using cell-mixed sheets of autologous fibroblast cells and peripheral blood mononuclear cells to treat refractory cutaneous ulcers.

BACKGROUND/AIMS: We invented a cell-mixed sheet consisting of autologous fibroblast cells and peripheral blood mononuclear cells (PBMNCs) to treat refractory cutaneous ulcers. These sheets secrete the growth factors needed throughout the wound healing process in animal models. METHODS: We performed this study as a pilot phase I clinical trial (UMIN-CTR: UMIN000031645). Fibroblast cells were isolated and cultured from the oral tissue, and PBMNCs were collected by apheresis. A cell-mixed sheet was prepared by co-culturing these collected cells for 3 days. The primary observation index was safety, including all adverse events. Additional observation indices were wound healing over 1, 3, and 6 months; wound healing rate at 7 days and 1, 3, and 6 months. RESULTS: Six patients with venous leg ulcers (VLUs) were enrolled in the study, including three patients who were treated with the cell-mixed sheet transplantation. One patient was excluded because no fibroblast cells grew from the oral tissue culture, and other two were excluded because the growth factor secreted from mixed-cell sheets did not reach the reference value. The VLUs of two patients who received the cell-mixed sheet transplantation healed, and the VLU in one patient decreased in size. CONCLUSIONS: This pilot study demonstrated that cell-mixed sheets might be a new topical intervention to treat VLUs. However, it was also suggested that this treatment might be limited when using autologous cells collected from patients with VLUs. Therefore, it may be necessary to use high-quality allogeneic cells instead of autologous cells to improve the feasibility of this treatment.

Treatment Results of Endovascular Aneurysm Repair Using the Parallel Stent-Graft Double D Technique for Distal Saccular Abdominal Aortic Aneurysms and Common Iliac Aneurysms.

BACKGROUND: Endovascular aneurysm repair (EVAR) using a bifurcated stent graft may involve technical challenges when aortic disease (aneurysm or dissection) consists of a length <70 mm between the inferior renal artery and aortic bifurcation or narrow aortic bifurcation that is common in asymmetric distal abdominal aortic aneurysms (AAAs) or iliac artery aneurysms (IAAs). We use EVAR with the double D technique (DDT-EVAR) for such cases, which involves straight type of stent grafts with same diameter in left and right that are deployed parallel to an aortic cuff that has been previously placed. In addition, DDT-EVAR can preserve the inferior mesenteric artery (IMA) for IAA. METHODS: DDT-EVAR was performed for 21 of 910 (2%) cases from April 2007 to April 2019 at our institution. The median patient age was 74 years (range, 52-85). Nineteen patients (90%) were men. Six patients (all saccular; 1 rupture) had AAAs, 12 had IAAs, and 3 had chronic type B aortic dissociation (TBAD) for re-entry closure. AAA and IAA had diameters of 45 mm (range, 34-71) and 34 mm (range, 25-58), respectively. An aortic cuff was used for 19 (90%) cases. Endurant II (Medtronic, Santa Rosa, CA) was used for 12 cases. The Excluder (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used for 7 cases. Endurant II was used for 20 cases, and the VBX (W.L. Gore & Associates, Inc) was used for 1 case as stent-graft limbs. RESULTS: The procedural success rate was 100%. The median operative time was 146 min (range, 88-324). IMA planned for preservation was successful for all 12 cases. Type I and type III endoleaks were not observed. With TBAD, flow to the false lumen decreased or disappeared, and no complications during the hospital stay were associated with the procedure. For 2 patients whose procedure involved Endurant II stent-graft limb, limb occlusions were observed postoperatively, and reintervention was required. No other patients required additional treatment at a median follow-up of 18 months (range, 4-50). CONCLUSIONS: DDT-EVAR is a safe and straightforward technique for the treatment of distal AAA, common iliac artery aneurysm, and TBAD. It may help preserve the IMA and internal iliac artery, even when it is impossible to preserve them with a bifurcated stent graft.

Extracellular Fluid Content in the Legs of Patients with Chronic Venous Disease.

BACKGROUND: This study aimed to determine the factors that affect the extracellular fluid (ECF) content in the legs of patients with chronic venous disease (CVD). METHODS: Bioimpedance analysis and air plethysmography (APG) were performed in 79 patients with CVD who visited our clinic between September 2016 and March 2019. The normal right legs (N) of 14 healthy volunteers were also reviewed for comparison. The ratio of ECF resistance (Re) of the leg to that of the arm (ReL/ReA) was used to express the ECF content in the tested leg. The severity of CVD was expressed using the clinical, etiological, anatomical, and pathophysiological (CEAP) classification. RESULTS: The ReL/ReA decreased as the CEAP class increased (N: median; 0.81 [range 0.66-0.95], C0-1: 0.79 [0.60-0.98], C2: 0.77 [0.56-1.08], C3: 0.67 [0.57-0.85], C4: 0.64 [0.44-0.89]). Older age, female sex, and CEAP class affected the ReL/ReA, but body mass index did not. The ReL/ReA did not correlate with the parameters that were derived from APG, including the venous filling index. CONCLUSIONS: We found that the ECF content in legs of patients with CVD might be primarily affected by patient-related factors and CEAP class, as opposed to venous hemodynamics.

Endovascular Aneurysm Repair With Re-entry Closure in a Patient With Abdominal Aortic Aneurysm Concomitant With Acute Type B Aortic Dissection.

INTRODUCTION: Abdominal aortic aneurysm (AAA) concomitant with acute aortic dissection is rare. CASE REPORT: An acute type B aortic dissection involving AAA in a 58 year old woman is described. Computed tomography angiography demonstrated that the false lumen of the abdominal aorta including the aneurysm remained patent, secondary to entry sites in the abdominal aorta, bilateral external iliac arteries, and a membrane tear of the left renal artery (LRA). The aneurysm was isolated by endovascular aneurysm repair and LRA stenting; all entry sites were occluded by endovascular treatment that included covered stenting of the LRA. Imaging performed three months after the procedure confirmed complete thrombosis of the false lumen and AAA sac shrinkage. DISCUSSION: Endovascular treatment with covered stents is reported as an alternative strategy for treatment of AAA concomitant with acute aortic dissection involving a visceral artery.

Allogeneic fibroblast sheets accelerate cutaneous wound healing equivalent to autologous fibroblast sheets in mice.

BACKGROUND/AIMS: This study sought to confirm the difference of the wound-healing effect, cell survival, and immune response between autologous fibroblast sheets and allogeneic fibroblast sheets. METHODS: Regarding wound healing, autologous or allogeneic fibroblast sheets were transplanted onto a mouse cutaneous wound healing model and the wound contraction rate was evaluated. The luciferase-expressing fibroblast sheet was prepared and the survival of the cell sheet was evaluated by IVIS® after autologous or allogeneic transplantation. Histological evaluation was performed at five and 14 days after transplantation. RESULTS: Allogeneic fibroblast-sheet transplantation showed significant wound contraction at the early phase of wound healing, which was equivalent to that seen with the autologous fibroblast sheets. Luminescence of the autologous and allogeneic luciferase-expressing fibroblast sheets peaked on Day 5, and no luminescence was observed on Day 13. In the allogeneic fibroblast-sheet transplant group, a significant accumulation of immune cells was observed in the healed tissue but not in the early stage of wound healing. CONCLUSION: The allogeneic fibroblast sheets showed comparable rates of cell survival and wound-healing effects to those of the autologous fibroblast sheets, despite the subsequent immunogenic response. This result supports the potential practical clinical application of scaffold-free allogeneic fibroblast sheets based on the paracrine effect.

Modulated Photocurrent Spectroscopy Study of the Electronic Transport Properties of Working Organic Photovoltaics: Degradation Analysis.

Electronic transport measurement using modulated photocurrent (MPC) spectroscopy is demonstrated herein in working organic photovoltaics (OPVs) before and after AM1.5G irradiation. OPVs with bulk heterojunction (BHJ) using prototypical donor and acceptor materials, poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1-2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl] = hieno [3-4-b]thiophenediyl]] (PTB7) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM), were fabricated. The OPVs had inverted structures (BHJs are formed on transparent conductive oxide substrates). The photovoltaic performance of PTB7:PC71BM OPVs was characterized and the best power conversion efficiency was obtained at PTB7 content of 40 wt%. Electron and hole mobility were determined with MPC spectroscopy in PTB7:PC71BM OPVs and were well balanced at PTB7 content of 40 wt%. Degradation of the photovoltaic performance of PTB7:PC71BM OPVs with PTB7 content of 40 wt% caused by AM1.5G irradiation was studied. MPC spectroscopy showed that the well-balanced mobility was not affected by AM1.5G irradiation. The degradation of OPVs was not due to changes in the electronic transport properties, but mainly to the reduced short circuit current (Jsc) and fill factor (FF). The origin of this reduction is discussed.