Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

Overview of single-port laparoscopic surgery for colorectal cancers: Past, present, and the future

Single-port laparoscopic surgery (SPLS) is implemented through a tailored minimal single incision through which a number of laparoscopic instruments access. Introduction of operation-customized port system, utilization of a camera without a separate external light, and instruments with different lengths has brought the favorable environment for SPLS. However, performing SPLS still creates several hardships compared to multiport laparoscopic surgery; a single-port system inevitably leads to clashing of surgical instruments due to crowding. To overcome such difficulties, investigators has developed novel concepts and maneuvers, including the concept of inverse triangulation and the maneuvers of pivoting, spreading out dissection, hanging suture, and transluminal traction. The final destination of SPLS is expected to be a completely seamless operation, maximizing the minimal invasiveness. Specimen extraction through the umbilicus can undermine cosmesis by inducing a larger incision. Therefore, hybrid laparoscopic technique, which combined laparoscopic surgical technique with natural orifice specimen extraction (NOSE) - i.e., transvaginal or transanal route-, has been developed. SPLS and NOSE seemed to be the best combination in pursuit of minimal invasiveness. In the near future, robotic SPLS with natural orifice transluminal endoscopic surgery’s way of specimen extraction seems to be pursued. It is expected to provide a completely or nearly complete seamless operation regardless of location of the lesion in the abdomen.

Innovative technique of needlescopic grasper-assisted single-incision laparoscopic common bile duct exploration:A comparative study

AIM: To investigate the safety and feasibility of needlescopic grasper-assisted single-incision laparoscopic common bile duct exploration(n SIL-CBDE) by comparing the surgical outcomes of this technique with those of conventional laparoscopic CBDE(CL-CBDE).METHODS: We retrospectively analyzed the clinical data of patients who underwent CL-CBDE or n SILCBDE for the treatment of common bile duct(CBD) stones between January 2000 and December 2014. For performing n SIL-CBDE, a needlescopic grasper was also inserted through a direct puncture below the right subcostal line after introducing a single-port through the umbilicus. The needlescopic grasper helped obtain the critical view of safety by retracting the gallbladder laterally and by preventing crossing or conflict between laparoscopic instruments. The gallbladder was then partially dissected from the liver bed and used for retraction. CBD stones were usually extracted through a longitudinal supraduodenal choledochotomy, mostly using flushing a copious amount of normal saline througha ureteral catheter. Afterward, for the certification of CBD clearance, CBDE was performed mostly using a flexible choledochoscope. The choledochotomy site was primarily closed without using a T-tube, and simultaneous cholecystectomies were performed.RESULTS: During the study period, 40 patients underwent laparoscopic CBDE. Of these patients, 20 underwent CL-CBDE and 20 underwent n SIL-CBDE. The operative time for n SIL-CBDE was significantly longer than that for CL-CBDE(238 ± 76 min vs 192 ± 39 min, P = 0.007). The stone clearance rate was 100%(40/40) in both groups. Postoperatively, the n SIL-CBDE group required less intravenous analgesic(pethidine)(46.5 ± 63.5 mg/kg vs 92.5 ± 120.1 mg/kg, P = 0.010) and had a shorter hospital stay than the CL-CBDE group(3.8 ± 2.0 d vs 5.1 ± 1.7 d, P = 0.010). There was no significant difference in the incidence of postoperative complications between the two groups.CONCLUSION: The results of this study suggest that n SIL-CBDE could be safe and feasible while improving cosmetic outcomes when performed by surgeons trained in conventional laparoscopic techniques.

Stratified computed tomography findings improve diagnostic accuracy for appendicitis

AIM: To improve the diagnostic accuracy in patients with symptoms and signs of appendicitis, but without confirmative computed tomography (CT) findings.

Technical and instrumental prerequisites for single-port laparoscopic solo surgery:state of art

With the aid of advanced surgical techniques and instruments, single-port laparoscopic surgery(SPLS) can be accomplished with just two surgical members: an operator and a camera assistant. Under these circumstances, the reasonable replacement of a human camera assistant by a mechanical camera holder has resulted in a new surgical procedure termed singleport solo surgery(SPSS). In SPSS, the fixation and coordinated movement of a camera held by mechanicaldevices provides fixed and stable operative images that are under the control of the operator. Therefore, SPSS primarily benefits from the provision of the operator's eye-to-hand coordination. Because SPSS is an intuitive modification of SPLS, the indications for SPSS are the same as those for SPLS. Though SPSS necessitates more actions than the surgery with a human assistant, these difficulties seem to be easily overcome by the greater provision of static operative images and the need for less lens cleaning and repositioning of the camera. When the operation is expected to be difficult and demanding, the SPSS process could be assisted by the addition of another instrument holder besides the camera holder.

Determination of surgical priorities in appendicitis based on the probability of undetected appendiceal perforation

AIM:To identify risk factors of actual appendiceal perforation when computed tomography(CT)scans suggest nonperforated appendicitis and accordingly determine surgical priority.METHODS:We collected database of 1362 patients who underwent an appendectomy for acute appendicitis between 2006 and 2013.A single radiologist selected1236 patients whose CT scans were suggestive ofnonperforated appendicitis.Patients were divided into 2 groups:actual nonperforation group and actual perforation group according to intraoperative and pathologic features.Comparison of the 2 groups were made using binary logistic regression.RESULTS:Of 1236 patients,90(7.3%)were found to have actual appendiceal perforation.Four risk factors related with actual appendiceal perforation were identified:body temperature≥37.6℃(HR=1.912,95%CI:1.161-3.149;P=0.011),out-ofhospital symptom duration≥72 h(HR=2.454,95%CI:1.292-4.662;P=0.006),age≥35 years(HR=3.358,95%CI:1.968-5.728;P<0.001),and appendiceal diameter on CT scan≥8 mm(HR=4.294,95%CI:1.034-17.832;P=0.045).Actual appendiceal perforation group showed longer operation time,later initiation of diet,longer use of parenteral narcotics,longer hospital stay,and higher incidence of postoperative complications(P<0.05).CONCLUSION:We proposed here new criteria to select patients with adverse clinical outcomes after appendectomy among the patients with radiologically nonperforated appendicitis.Surgical appendectomy outcomes could be improved by determining the surgical priority according to our criteria.

Ameliorating liver fibrosis in an animal model using the secretome released from miR-122-transfected adipose-derived stem cells

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,called secretome,rather than cells,has been evaluated for overcoming the limitations of cell-based therapy,while maintaining its advantages.However,the use of na?ve secretome may not fully satisfy the specificity of each disease.Therefore,it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use na?ve secretome.AIM To determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells(ASCs).METHODS We collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122(MCM)and compared their antifibrotic effects with those of the na?ve secretome(CM).MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis,and their therapeutic potentials were compared.RESULTS MCM infusion provided higher therapeutic potential in terms of:(A)Reducing collagen content in the liver;(B)Inhibiting proinflammatory cytokines;and(C)Reducing abnormally elevated liver enzymes than the infusion of the na?ve secretome.The proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the na?ve secretome.CONCLUSION We could,thus,conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the na?ve secretome.Because miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome,it could be considered as an enhanced method for reinforcing secretome effectiveness.

Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether

BACKGROUND The use of methyl-tertiary butyl ether(MTBE)to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy.The adverse effects of MTBE are largely attributed to its low boiling point,resulting in a tendency to evaporate.Therefore,if there is a material with a higher boiling point and similar or higher dissolubility than MTBE,it is expected to be an attractive alternative to MTBE.AIM To determine whether tert-amyl ethyl ether(TAEE),an MTBE analogue with a relatively higher boiling point(102°C),could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity.METHODS The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents.The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control(dimethyl sulfoxide)-treated gallstones,after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones.RESULTS The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%,56.5%and 38.75%for cholesterol,mixed,and pigmented gallstones,respectively,which represented a 1.2-,1.4-,and 1.3-fold increase in dissolubility compared to that of MTBE.In the in vitro experiment,the 24 h-dissolubility of TAEE was 71.7%and 63.0%for cholesterol and pigmented gallstones,respectively,which represented a 1.4-and 1.9-fold increase in dissolubility compared to that of MTBE.In addition,the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE.CONCLUSION We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE.As such,TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the naïve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected to open a new way of developing various specific therapeutics based on the high plasticity and responsiveness of MSCs.

Single-port laparoscopic surgery for sigmoid volvulus

AIM:To report our experience with single-port laparoscopic surgery(SPLS)for sigmoid volvulus(SV).METHODS:Between October 2009 and April 2013,10patients underwent SPLS for SV.SPLS was performed transumbilically or through a predetermined stoma site.Conventional straight and rigid-type laparoscopic instruments were used.After intracorporeal,segmental resection of the affected sigmoid colon,the specimen was extracted through the single-incision site.Patientdemographics and perioperative data were analyzed.RESULTS:SPLS for SV was successful in all 10 patients(4,resection and primary anastomosis;6,Hartmann’s procedure).The median operative time and postoperative hospitalization period were 168(range,85-315)min and 6.5(range,4-29)d,respectively.No intraoperative complications were noted;there were 2 postoperative complications,including 1 anastomotic leak.CONCLUSION:SPLS was a safe and feasible therapeutic approach for SV,when performed by a surgeon experienced in conventional laparoscopic surgery.