Intracerebral hemorrhage due to vasculitis following COVID-19 vaccination: a case report.

Several vaccines have been approved worldwide for the prevention of morbidity and mortality against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of these vaccines has raised concerns regarding their adverse effects. Herein, we report the first case of intracerebral hemorrhage (ICH) due to vasculitis after the first dose of mRNA vaccine (BNT162b2, Pfizer/BioN-Tech). Although this case cannot demonstrate a direct relationship between COVID-19 vaccination and vasculitis, the clinical and histological features of this patient are highly consistent with the adverse effects of COVID-19 vaccine.

Lipomatosis of axillary lymph nodes in a cynomolgus monkey (Macaca fascicularis).

Lipomatosis of lymph nodes is defined as the replacement of the lymphatic parenchyma by adipose tissue which grows in the node from the hilus toward the cortical zone. In humans, it is considered as part of the normal aging process and is common in obese patients, but there are no reports in non-human primates. In this report, we describe the first case of lymph node lipomatosis in the bilateral axillary lymph nodes of a young adult cynomolgus monkey. Macroscopically, there were no apparent abnormalities in the axillary lymph nodes on either side, and their volumes were unchanged. At the cut surface, pale yellow fat-like tissue was observed in the medullary area. Histopathologically, well differentiated adipocytes replaced a large part of the lymphatic parenchyma in the area from the hilus to the medulla without any malignant findings. Based on these findings, the patient was diagnosed with lipomatosis of the lymph nodes.

Prognostic Implications of Non-Invasive Vascular Function Tests in High-Risk Atherosclerosis Patients.

BACKGROUND: The aim of this study was to assess the role of clinically available vascular function tests as predictors of cardiovascular events and decline in kidney function. METHODS AND RESULTS: One hundred and fourteen patients who had at least 2 cardiovascular risk factors were recruited for vascular function assessment including ankle-brachial blood pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and flow-mediated vasodilatation (%FMD). During a median period of 51 months, 35 patients reached the primary endpoint (29 cardiovascular events and 6 cardiac deaths), and 30 patients reached the secondary endpoint (decline in kidney function: defined as a 5% per year decline of estimated glomerular filtration rate). In sequential Cox models, a model on the basis of the Framingham risk score, hemoglobin, and high-sensitivity C-reactive protein (chi-squared, 16.6) was improved by the ABI (chi-squared: 21.5; P=0.047). The baPWV (hazard ratio: 1.42 per 1 SD increase; P=0.025) and the CAVI (hazard ratio: 1.52 per 1 SD increase; P=0.040) were associated with the secondary endpoint. The %FMD was only slightly associated with the primary and secondary endpoints. CONCLUSIONS: Both ABI and baPWV are significantly associated with future cardiovascular events in high-risk patients with cardiovascular disease. The predictive capabilities of these parameters are greater than that of other parameters in this cohort.

Optimal Analysis of Left Atrial Strain by Speckle Tracking Echocardiography: P-wave versus R-wave Trigger.

BACKGROUND: Left atrial (LA) strain analysis using speckle tracking echocardiography is useful for assessing LA function. However, there is no established procedure for this method. Most investigators have determined the electrocardiographic R-wave peak as the starting point for LA strain analysis. To test our hypothesis that P-wave onset should be used as the starting point, we measured LA strain using 2 different starting points and compared the strain values with the corresponding LA volume indices obtained by three-dimensional (3D) echocardiography. METHODS: We enrolled 78 subjects (61 ± 17 years, 25 males) with and without various cardiac diseases in this study and assessed global longitudinal LA strain by two-dimensional speckle tracking strain echocardiography using EchoPac software. We used either R-wave peak or P-wave onset as the starting point for determining LA strains during the reservoir (Rres, Pres), conduit (Rcon, Pcon), and booster pump (Rpump, Ppump) phases. We determined the maximum, minimum, and preatrial contraction LA volumes, and calculated the LA total, passive, and active emptying fractions using 3D echocardiography. RESULTS: The correlation between Pres and LA total emptying fraction was better than the correlation between Rres and LA total emptying fraction (r = 0.458 vs. 0.308, P = 0.026). Pcon and Ppump exhibited better correlation with the corresponding 3D echocardiographic parameters than Rcon (r = 0.560 vs. 0.479, P = 0.133) and Rpump (r = 0.577 vs. 0.345, P = 0.003), respectively. CONCLUSIONS: LA strain in any phase should be analyzed using P-wave onset as the starting point rather than R-wave peak.

Correlation Between Arteriosclerosis and Periodontal Condition Assessed by Lactoferrin and α1-Antitrypsin Levels in Gingival Crevicular Fluid.

Patients with periodontal disease exhibit exacerbated atherosclerosis, aortic stiffness, or vascular endothelial dysfunction. However, in a recent scientific statement, the American Heart Association noted that neither has periodontal disease been proven to cause atherosclerotic vascular disease nor has the treatment of periodontal disease been proven to prevent atherosclerotic vascular disease. Therefore, the aim of the present study was to examine the correlation between periodontal condition and arteriosclerosis in patients with coronary artery disease (CAD), which is usually accompanied by systemic arteriosclerosis.We measured levels of gingival crevicular fluid lactoferrin (GCF-Lf) and α1-antitrypsin (GCF-AT) in 72 patients (67 ± 8 years, 56 men) with CAD. Furthermore, we evaluated the maximum intima-media thickness (max IMT) and plaque score of the carotid arteries as well as brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) of the brachial artery, each of which is a parameter for determining arteriosclerosis status. The average level of GCF-Lf was 0.29 ± 0.36 µg/mL and that of GCF-AT was 0.31 ± 0.66 µg/mL, with significant correlation between the two (r = 0.701, P < 0.001). No significant difference in GCF-Lf and GCF-AT levels was observed between patients with single-, double-, and triple-vessel CAD. There were no significant correlations between the arteriosclerosis parameters (ie, max IMT, plaque score, baPWV, and FMD) and GCF-Lf or GCF-AT.No correlation between the GCF biomarkers and the severity of arteriosclerosis was detected. This result may suggest that worsening of the periodontal condition assessed by GCF biomarkers is not a major potential risk factor for arteriosclerosis.

Augmentation index does not reflect risk of coronary artery disease in elderly patients.

BACKGROUND: Augmentation index (AI) has been used as a clinical index of arterial stiffness and has been reported to be an independent predictor of cardiovascular events, but some investigators have reported that AI is not a useful marker to identify coronary artery disease (CAD) in elderly patients. The majority of CAD patients are elderly people, therefore the aim of this study was to examine whether AI is a useful marker to identify the risk of CAD. METHODS AND RESULTS: A total of 120 patients (69±10 years of age; 83 male) who underwent cardiac catheterization for suspected CAD were enrolled. Invasive central blood pressure (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects consisted of 99 patients with CAD and 21 patients without CAD. There was no significant difference in AI between the CAD and the non-CAD groups (24±10 vs. 24±14%). Non-invasive systolic central BP was lower than the invasive systolic central BP (115±18 vs. 130±23 mmHg, P<0.001) in all patients. Non-invasive diastolic central BP was greater than the invasive diastolic central BP (67±10 vs. 63±10 mmHg, P<0.001). CONCLUSIONS: In elderly patients, AI may not be a useful marker to identify CAD.

Massive tricuspid regurgitation due to pacemaker-lead puncture of the tricuspid valve: successful diagnosis by 3-dimensional echocardiography.

An 83-year-old woman presented to our echocardiographic center with symptoms of right heart failure. A dual-chamber DDDR pacemaker had been implanted 9 years earlier. Two-dimensional echocardiography revealed right atrial and ventricular enlargement and massive tricuspid regurgitation with immobilization of the anterior leaflet of the tricuspid valve. Three-dimensional transesophageal echocardiography showed that the pacemaker lead had punctured the leaflet. These echocardiographic findings were confirmed during surgery. The pacemaker lead was transected and removed, and pericardial patch closure of the leaflet hole and tricuspid annuloplasty were performed. The mechanism of regurgitation was elucidated by real-time three-dimensional echocardiography, and surgical repair was straightforward.

Microbial mat compositions and localization patterns explain the virulence of black band disease in corals.

Black band disease (BBD) in corals is characterized by a distinctive, band-like microbial mat, which spreads across the tissues and often kills infected colonies. The microbial mat is dominated by cyanobacteria but also commonly contains sulfide-oxidizing bacteria (SOB), sulfate-reducing bacteria (SRB), and other microbes. The migration rate in BBD varies across different environmental conditions, including temperature, light, and pH. However, whether variations in the migration rates reflect differences in the microbial consortium within the BBD mat remains unknown. Here, we show that the micro-scale surface structure, bacterial composition, and spatial distribution differed across BBD lesions with different migration rates. The migration rate was positively correlated with the relative abundance of potential SOBs belonging to Arcobacteraceae localized in the middle layer within the mat and negatively correlated with the relative abundance of other potential SOBs belonging to Rhodobacteraceae. Our study highlights the microbial composition in BBD as an important determinant of virulence.

Isoproterenol loading transesophageal echocardiography in atrial fibrillation.

In patients with sludge or severe spontaneous echo contrast (SEC) in the left atrial appendage (LAA), cases with isoproterenol loading transesophageal echocardiography (ISP-TEE) have been reported to identify the presence of thrombus in the LAA. This study aimed to assess the validity and hemodynamic changes of ISP-TEE in the LAA. We prospectively enrolled patients with atrial fibrillation (AF) who underwent ISP-TEE. The degree of sludge/SEC was categorized as being either absent (grade 0), mild SEC (grade 1), moderate SEC (grade 2), severe SEC or sludge (grade 3). The hemodynamic evaluation was performed by measuring LAA flow velocity, LAA tissue Doppler imaging (LAA-TDI) velocity, and pulmonary vein systolic forward flow velocity (PVS). In total, 35 patients (mean age 71 ± 7 years; 71% male) underwent ISP-TEE. Among 35 patients, 30 patients had grade 3 or 2 SEC, 5 patients had grade 1 SEC. After ISP loading, 23 patients (66% of all patients) showed improved sludge/SEC and one patient was diagnosed with thrombus in the LAA. There were 25 patients with grade 1 SEC, or no SEC (classified as Group1), 10 patients had residual sludge or grade 2 to 3 SEC (classified as Group2) after ISP administration. LAA flow, LAA-TDI, and PVS velocities were significantly higher in group 1 than in group 2 after ISP administration. There was no complication during the examination and after 24 h and 3 months. ISP infusion may be a potential tool to recognize LAA thrombus under the sludge/SEC during TEE in AF.

Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles.

Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte-endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

Digital workflows for pathological assessment of rat estrous cycle stage using images of uterine horn and vaginal tissue.

Assessment of the estrous cycle of mature female mammals is an important component of verifying the efficacy and safety of drug candidates. The common pathological approach of relying on expert observation has several drawbacks, including laborious work and inter-viewer variability. The recent advent of image recognition technologies using deep learning is expected to bring substantial benefits to such pathological assessments. We herein propose 2 distinct deep learning-based workflows to classify the estrous cycle stage from tissue images of the uterine horn and vagina, respectively. These constructed models were able to classify the estrous cycle stages with accuracy comparable with that of expert pathologists. Our digital workflows allow efficient pathological assessments of the estrous cycle stage in rats and are thus expected to accelerate drug research and development.

Estimation of the distribution of intravenously injected adipose tissue-derived stem cells labeled with quantum dots in mice organs through the determination of their metallic components by ICPMS.

Adipose tissue-derived stem cells (ASCs) have shown promise in cell therapy because of their ability to self-renew damaged or diseased organs and easy harvest. To ensure the distribution and quantification of the ASCs injected from tail vein, several whole-body imaging techniques including fluorescence optical imaging with quantum dots (QDs) have been employed, but they may suffer from insufficient sensitivity and accuracy. Here, we report quantitative distribution of ASCs in various organs (heart, lung, liver, spleen, and kidney) of mice, which were intravenously injected with QDs-labeled ASCs (QDs-ASCs), through the detection of QDs-derived metallic components by inductively coupled plasma mass spectrometry (ICPMS). For accurate and precise determination, each organ was harvested and completely digested with a mixture of HNO(3) and H(2)O(2) in a microwave oven prior to ICPMS measurement, which was equipped with a microflow injection system and a laboratory-made capillary-attached micronebulizer. After optimization, 16 elements including major components (Cd, Se, and Te) of QDs and essential elements (Na, K, Mg, Ca, P, S, Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo) were successfully determined in the organs. As compared to untreated mice, QDs-ASCs-treated mice showed significantly higher levels of Cd and Te in all organs, and as expected, the molar ratio of Cd to Te in each organ was in good agreement with the molar composition ratio in the QDs. This result indicates that the increment of Cd (or Te) can be used as a tracer for calculating the distribution of ASCs in mice organs. As a result of the calculation, 36.8%, 19.1%, 0.59%, 0.49%, and 0.25% of the total ASCs injected were estimated to be distributed in the liver, lung, heart, spleen, and kidney, respectively.

Mechanism of photofrin-enhanced ultrasound-induced human glioma cell death.

BACKGROUND: Low-intensity ultrasound showed tumor cell killing by a non-thermal effect in human leukemia cells. The aim of our study was to investigate the efficacy of low-intensity ultrasound on malignant astrocytic tumor cells with the photosensitizer, Photofrin, which is taken up by the cell surface receptor, low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR). MATERIALS AND METHODS: Cells were sonicated with continuous wave ultrasound with or without the presence of Photofrin (75 mg/ml) at an intensity of 0.3 W/cm(2) for a duration of 5, 15, or 30 s. RESULTS: Ultrasound alone induced instant cell killing immediately after sonication in both U251MG and U105MG malignant gliomas cells. In U251MG cells, which expressed LRP/alpha2MR, significant enhancement of cell killing was observed following Photofrin pretreatment, 52.7+/-17.5%, 13.0+/-4.6% and 3.9+/-0.9% for 5, 15, and 30 s respectively (p<0.05). This enhancement of cell killing was abolished by preincubation with receptor-associated protein (RAP) which binds specifically to LRP/alpha2MR. This enhancement by Photofrin was not achieved in U105MG which did not express LRP/alpha2MR. U251MG cells accumulated 2.43+/-0.25 Photofrin mg/mg protein, which significantly decreased with RAP pretreatment (1.38+/-0.22 Photofrin mg/mg protein) (p<0.05). U105MG cells accumulated 1.31+/-0.16 Photofrin mg/mg protein, which was significantly less than in U251MG cells. Photofrin uptake was not altered by RAP pretreatment in U105MG cells. U251MG cells exposed to ultrasound in the presence of Photofrin showed multiple surface pores and dimple-like craters. CONCLUSION: This is the first report to demonstrate the usefulness of low-intensity ultrasound for the cell killing of malignant glioma cells. Antitumor activity might be enhanced by combination with photosensitizer, which is transported by cell surface LRP/alpha2-MR to some degree.

Effects of focused ultrasound sonodynamic treatment on the rat blood-brain barrier.

BACKGROUND: Ultrasound has recently been applied to the treatment as well as the diagnosis of various pathologies, and its antitumor effects in the treatment of human cancer and experimental models of cancer have been demonstrated. In addition, it is possible that certain photosensitizers will enhance the antitumor effects of ultrasound. However, very few studies have been reported on how the blood-brain barrier is affected by sonodynamic therapy. The purpose of this study was to evaluate disruption of the blood-brain barrier with focused ultrasound with a photosensitizer, for clinical application of sonodynamic therapy to brain tumors. MATERIALS AND METHODS: Rat brains were subjected to focused ultrasound irradiation via a transducer with or without prior intravenous injection of photosensitizer, and lesions were examined histologically by electron microscopy. RESULTS: Electron microscopically, swelling of astroglial processes, denatured cells, protoplasm of endothelial cells, and mitochondria were observed in the center and border of regions of ultrasonic irradiation. There were numerous pinocytotic vesicles in the cytoplasm of the endothelial cells. In addition, disruption of the cytoplasmic membrane of endothelial cells and astroglia was found in these regions. CONCLUSION: These findings suggest that sonodynamic therapy with a photosensitizer affects the blood-brain barrier, and that blood vessel permeability increases not only as a result of destruction of the blood-brain barrier but also by disruption of the cytoplasmic membrane of endothelial cells.

Emphysematous cystitis in a chemically-induced diabetic dog.

Emphysematous cystitis is a rare disorder caused by bacterial infection and characterized by gas accumulation within the bladder wall with cyst formation. This report describes the histopathological characteristics of emphysematous cystitis found in a diabetic female beagle induced by streptozotocin and alloxan. Macroscopically, multiple cyst-like structures were observed on the cut surface of the urinary mucosa. During fixation, small specimens cut from the mucosa floated on the surface of the fixative solution. Histopathologically, multiple cysts were lined with a single layer of flattened cells found to be immunohistochemically positive for vimentin, partially positive for α-smooth muscle actin or macrophage scavenger receptor, class A, and thought to be myofibroblasts, fibroblasts or macrophages. Multinucleated giant cells were observed around the cysts, and gram-negative short bacilli were observed in the lumen of the urinary bladder. From these findings, this case was diagnosed as emphysematous cystitis.

Double-crescent sign as a predictor of chronic subdural hematoma recurrence following burr-hole surgery.

OBJECTIVE: Subdural hygroma has been reported as a causative factor in the development of a chronic subdural hematoma (CSDH) following a head trauma and/or neurosurgical procedure. In some CSDH cases, the presence of a 2-layered space delineated by the same or similar density of CSF surrounded by a superficial, residual hematoma is seen on CT imaging after evacuation of the hematoma. The aims of the present study were to test the hypothesis that the double-crescent sign (DCS), a unique imaging finding described here, is associated with the postoperative recurrence of CSDH, and to investigate other factors that are related to CSDH recurrence. METHODS: The authors retrospectively analyzed data from 278 consecutive patients who underwent single burr-hole surgery for CSDH between April 2012 and March 2017. The DCS was defined as a postoperative CT finding, characterized by the following 2 layers: a superficial layer demonstrating residual hematoma after evacuation of the CSDH, and a deep layer between the brain's surface and the residual hematoma, depicted as a low-density space. Correlation of the recurrence of CSDH with the DCS was evaluated by multivariate logistic regression modeling. The authors also investigated other classic predictive factors including age, sex, past history of head injury, hematoma laterality, anticoagulant and antiplatelet therapy administration, preoperative hematoma volume, postoperative residual hematoma volume, and postoperative brain reexpansion rate. RESULTS: A total of 277 patients (320 hemispheres) were reviewed. Fifty (18.1%) of the 277 patients experienced recurrence of CSDH within 3 months of surgery. CSDH recurred within 3 months of surgery in 32 of the 104 hemispheres with a positive DCS. Multivariate logistic analyses revealed that the presence of the DCS (OR 3.36, 95% CI 1.72-6.57, p < 0.001), large postoperative residual hematoma volume (OR 2.88, 95% CI 1.24-6.71, p = 0.014), anticoagulant therapy (OR 3.03, 95% CI 1.02-9.01, p = 0.046), and bilateral hematoma (OR 3.57, 95% CI 1.79-7.13, p < 0.001) were significant, independent predictors of CSDH recurrence. CONCLUSIONS: In this study, the authors report that detection of the DCS within 7 days of surgery is an independent predictive factor for CSDH recurrence. They therefore advocate that clinicians should carefully monitor patients for postoperative DCS and subsequent CSDH recurrence.

Cell surface heparan sulfate proteoglycans mediate the internalization of PDX-1 protein.

Although islet transplantation is a promising therapeutic option for the treatment of type 1 diabetes, the shortage of suitable donor tissues remains a major obstacle. Pancreatic stem/progenitor cells residing within the ductal epithelium have been used to generate human islet-like clusters, but there is no efficient strategy for facilitating differentiation of progenitor cells into insulin-producing cells. A previous study reported that exogenous PDX-1 protein can be transduced into pancreatic stem/progenitor cells and induce differentiation of the cells into insulin-producing cells without requiring gene transfer technology. This study provides genetic and biochemical evidence that cell membrane heparan sulfate proteoglycans are required for extracellular PDX-1 internalization. Heparin, one of the soluble glycosaminoglycans (GAGs), inhibited PDX-1 internalization, while chondroitin sulfate A, B, and C caused only very limited inhibition. Cell treatment with heparinase-III demonstrated impaired PDX-1 internalization, while treatment with chondroitinase ABC, or with chondroitinase AC, was completely ineffective in inhibiting PDX-1 internalization. Different mutant cell lines originating from CHO K1 cells and defective in GAG biosynthesis were also examined. PDX-1 internalization was significantly reduced in both pgs A-745 mutant cells, which are defective in a enzyme that initiates GAG synthesis, and pgs B-618 cells, which produce about 15% of the amount of GAGs synthesized by wild-type cells. These data indicate that cell-surface heparan sulfate proteoglycans are required for PDX-1 internalization and that PDX-1 protein transduction could be a valuable strategy for inducing insulin expression in pancreatic stem/progenitor cells without requiring gene transfer technology.

Cryopreservation of mouse adipose tissue-derived stem/progenitor cells.

Adipose tissue-derived stem/progenitor cells (ASCs) have been reported to differentiate not only into mesodermal cells such as osteoblasts, chondorocytes, and adipocytes, but also to endodermal cells such as hepatocytes and insulin-expressing cells. These stem/progenitor cells are expected to be used for variety of regenerative therapies. This study demonstrates the viability and the adipo/osteogenic potential of cryopreserved ASCs using seven cryopreservation solutions, including 10% DMSO, Cell Freezing Medium-DMSO, Cell Freezing Medium-Glycerol, Cell Banker 1, Cell Banker 1+, Cell Banker 2, and CP-1. ASCs were obtained from mouse subcutaneous adipose tissue. The viability of the cryopreserved ASCs was over 90% with Cell Banker 2 preservation, approximately 90% with Cell Banker 1, Cell Banker 1+, or CP-1 preservation, and less than 80% for 10% DMSO, Cell Freezing Medium-DMSO, or Cell Freezing Medium-Glycerol preservation. No difference in the adipo/osteogenic potential was found between cells with or without cryopreservation in Cell Banker 2. These data suggests that Cell Banker 2 is the most effective cryopreservation solution for ASCs and that cryopreserved as well as noncryopreserved ASCs could be applied for regenerative medicine.

Recombinant sendai virus-mediated gene transfer to adipose tissue-derived stem cells (ASCs).

Adipose tissue-derived stem cells (ASCs) are expected to have clinical applications as well as other stem cells, because ASCs can be obtained safely from adult donors and used in autologous therapies without concern about rejection and the need for immunosuppression. However, the use of gene transfer with Sendai virus (SeV) vectors, which can efficiently introduce foreign genes without toxicity into several cells, with ASCs has not yet been investigated. This study documents on the use of SeV vectors for gene transfer to ASCs. The dose-dependent GFP expression of ASCs transfected with SeV vectors after 48 h of culture at 37 degrees C was first evaluated. Next, the cellular toxicity of ASCs transfected with SeV vectors was verified. In addition, SeV vectors were compared with adenovirus (AdV) vectors. Finally, the time-dependent GFP expression of ASCs transfected with SeV vectors was evaluated. The results showed that transfection of ASCs with SeV vectors results in more efficient expression of transgene (GFP expression) in the ASCs than with AdV vectors after 48 h of culture at 37 degrees C. Moreover, while the transfection of ASCs with AdV vectors at high MOIs was cytotoxic (a lot of transfected cells died) that of ASCs with SeV vectors at high MOIs was not necessarily cytotoxic. In addition, the preservation of multilineage ASCs transfected with SeV was observed. In conclusion, this is the first report describing the successful use of SeV-mediated gene transfer in ASCs, and the results indicate that SeV may thus provide advantages with respect to safety issues in gene therapy.