MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC-Exo) for the prevention of esophageal stenosis after ESD in a porcine model. RESULTS: Pigs were randomly assigned into (1) ChGelMSC-Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGelMSC-Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFß1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. CONCLUSIONS: Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.

Randomized double-blinded prospective trial of fibrin sealant spray versus mechanical stapling in laparoscopic total extraperitoneal hernioplasty.

OBJECTIVE: The aim of the current study was to compare the clinical outcomes of mesh fixation with fibrin sealant (FS) spray or mechanical stapling (MS) in laparoscopic total extraperitoneal hernioplasty (TEP). BACKGROUND: The most appropriate method of mesh fixation is uncertain. METHODS: Between June 2007 and June 2011, consecutive patients with primary reducible unilateral inguinal hernia who underwent day-case laparoscopic TEP were recruited. Outcome parameters included the incidence of acute and chronic pain, recurrence rates, morbidity rates, analgesic requirements, quality-of-life (QOL) scores, and direct cost. RESULTS: During the study period, 130 patients were included in the study. Patients in the MS group had significantly worse pain scores on the day after operation (P = 0.006). Analgesic requirements were similar between the 2 groups (P = 0.558). At 6 months, no significant differences in the incidence of chronic pain were observed (at rest, after coughing or cycling). The incidence of seroma formation was similar between the 2 groups (P = 0.64), and no recurrences were observed at 1 year. No differences in the QOL scores were detected. The direct cost of the entire hospitalization in the FS group was less expensive (P < 0.001). CONCLUSIONS: FS and MS are both effective methods of providing mesh fixation. FS was associated with reduced acute pain but not chronic pain. The rates of seroma formation were similar. However, the use of FS for mesh fixation was less expensive. [corrected].