Deniz Filinte

Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma

New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P<0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P<0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (P<0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma.

Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma.

New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5×10(5) ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.

The effects of the centrifugation speed on the survival of autogenous fat grafts in a rat model

Abstract Purpose The most important problem in fat transplantation is the durability, which is closely associated with the applied technique. This study includes the comparison of different centrifugation speeds on the survival of autogenous fat grafts in rats. Materials and methods Forty-nine Sprague-Dawley rats were divided into seven groups and the left inguinal fat pad was extracted and re-implanted under the scalp after performing appropriate preparation processes. In the first group the fatty tissue was re-implanted in en-bloc fashion and in the second group it was re-implanted after trimming. After trimming, centrifugation with a G-force of 111.8 (1000 rpm) was performed in the third group, 447.2 (2000 rpm) in the fourth group, 1006.2 (3000 rpm) in the fifth group, 1788.8 (4000 rpm) in the sixth group, and 2795 (5000 rpm) in the seventh group for 4 minutes. The fat grafts were taken after 3 months and histopathological and statistical evaluations were performed. Results The rate of viable fat grafts was significantly higher in the 4th and 5th groups comparing to the first three groups. Total weight and volume amounts of the 4th and 5th groups were also significantly higher comparing to the first three groups. Conclusion Maximal long-term durability and fat cell viability results were obtained in the groups with 2000 rpm or 447.2 G-force/4 minutes and 3000 rpm or 1006.2 G-force/4 minutes centrifugation speed, indicating that 4 minutes centrifugation with an average G-force of 698.75 or 2500 rpm provides the best results for the survival of autogenous fat grafts.

Effects of Deferoxamine on Fat Graft Survival

The most important problem in fat transplantation is the unpredictable rates of resorption. Deferoxamine (DFO) is an iron-chelating agent with many useful functions including stimulating angiogenesis and antioxidant nature. The purpose of the study is to evaluate the effects of DFO on fat graft viability in rat model. A total of 24 Wistar rats were divided into three groups and 0.5 g of the left inguinal fat pad was extracted. In control group, fat grafts were implanted to the parascapular area without performing any procedure. In sham group, they were implanted in 0.2 mL saline solution followed by serial saline injections for 1 month. In the study group, fat grafts were implanted in 0.2 mL saline solution and 300 mg DFO followed by serial DFO injections for 1 month. At the postoperative second month, fat grafts were taken back and sent for histopathologic examination. The weight measurements of biopsy specimens in the study group demonstrated significantly higher than in the other two groups. Inflammation and fibrosis rates were also found to be significantly higher in the study group compared with the other groups; however, no significant difference in the apoptosis rates was detected between the groups. Fat grafts enriched with DFO showed significant increase in fatty tissue content in the study group compared with the control and sham groups. DFO increases the fat graft survival in rats and it may be a useful addition in autologous fat grafting procedures to increase fat graft viability and obtain maximal long-term durability.

Locally Advanced Pseudopapillary Neoplasm of the Pancreas in a Male Patient: A Case Report

CONTEXT Solid pseudopapillary tumor of the pancreas is a rare neoplasm, predominantly observed in young women and with greatest incidence in the second and third decade. Although large at the time of diagnosis, it has clinically good behavior. The occurrence of infiltrating varieties of solid pseudopapillary tumors is very rare. CASE REPORT We report the case of a 48-year-old man with a giant mass in the pancreas, incidentally discovered during an abdominal ultrasonography. The mass was later investigated using multidetector computed tomography and magnetic resonance imaging. The lobulated lesion had cystic-necrotic appearances which lead the radiologists to suggest the possibility of either a gastrointestinal stromal tumor or a pancreatic cancer. The patient was operated. Operative signs showed that the tumor invaded the splenic hilum and mesentery of transverse colon. En-block resection of pancreas, spleen and transverse colon was performed as the mass was thought to be a locally advanced pancreas tumor. Pathological diagnosis reported a solid pseudopapillary tumor. CONCLUSION Although solid pseudopapillary tumor is considered a rare tumor, with a very rare rate of locally infiltrating variety, and rarely presents in males, it must be kept in mind while making the differential diagnosis of cystic pancreatic lesions to begin appropriate clinical management.

Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model

OBJECTIVE The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model. METHODS Thirty female Sprague-Dawley underwent experimental pharyngoesophagotomy and were grouped depending on the material used for pharyngocutaneous fistula closure: group I, which received primary sutures alone, group II, which received bacterial cellulose alone; and group III, which received both. After 7 days, the rats were sacrificed. Pharyngocutaneous fistula development was assessed, the gross wound was inspected, and histological examination was conducted. RESULTS Pharyngocutaneous fistulae developed in 12 rats (41%) in all: 6 from group I (21%), 4 from group II (14%) and 2 from group III (7%). CONCLUSION Fibroblast density and inflammatory cell infiltration were significantly greater in group III than group I. We concluded that bacterial cellulose may be useful for pharyngocutaneous fistula closure.

Postoperative Atrial Fibrillation after Coronary Artery Bypass Grafting Surgery: A Two-dimensional Speckle Tracking Echocardiography Study

BACKGROUND Postoperative atrial fibrillation (POAF) may develop after coronary artery bypass grafting (CABG). The aim of the study was to explore the relationship between preoperative left atrial function and atrial fibrosis and POAF after CABG. METHODS Forty-eight consecutive patients undergoing CABG (mean age: 61.6±8.9 years, 39 male) were included. All patients were in sinus rhythm during surgery. Patients were followed by continuous electrocardiography monitoring and daily electrocardiogram. Left atrial function was assessed by both conventional and speckle tracking echocardiography. Atrial fibrosis was determined by samples taken from right atrium. RESULTS Postoperative atrial fibrillation was detected in 13 patients. Female sex and number of bypassed vessels were significantly higher and cardiopulmonary bypass time was significantly longer in patients with POAF. Left atrial volume index (LAVI) was significantly higher while left atrial reservoir strain was significantly lower in POAF patients. The percentage of patients with severe fibrosis was higher in the POAF group. Regression analysis revealed fibrosis and LAVI as independent predictors of POAF. Left atrial volume index ≥36mL/m(2) predicted POAF with a sensitivity of 84.6% and specificity of 68.6% in our cohort. CONCLUSION Patients who developed POAF after CABG had more fibrosis, increased LAVI and lower left atrial reservoir strain. Preoperative echocardiography might be helpful in discriminating these patients.

Role of Tyrosine Kinase Inhibition with Imatinib in an Encapsulating Peritoneal Sclerosis Rat Model

Background: Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model. Methods: We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0–3 followed by a peritoneal rest period between weeks 3–6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0–3 followed by 50 mg/kg imatinib mesylate through weeks 3–6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-β1 (TGF-β1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry. Results: An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-β1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-β1-positivity on immunohistochemistry between the groups. Conclusions: Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.