Human amniotic MSCs-mediated anti-inflammation of CD206hiIL-10hi macrophages alleviates isoproterenol-induced ventricular remodeling in mice.

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases. OBJECTIVE: This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR). METHODS: hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro. RESULTS: hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, the CM derived from hAMSCs pretreated with RAW264.7-CM markedly inhibited the expressions of fibrogenesis genes such as αSMA and COL3 in 3T3 cells. CONCLUSION: Our results demonstrated that hAMSCs effectively alleviated ISO-induced cardiac hypertrophy and fibrosis, and improved the cardiac functions in mice, and the underlying mechanisms might be related to inhibiting the inflammation and fibrosis during the ventricular remodeling through promoting the polarization of CD206hiIL-10hi macrophages in heart tissues. Our study strongly suggested that by taking the advantages of the potent immunosuppressive and anti-inflammatory effects, hAMSCs may provide an alternative therapeutic approach for prevention and treatment of VR clinically.

Potential application of ultrasound-guided thermal ablation in rare liver tumors.

BACKGROUND: With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited. METHODS: We analyzed twelve pathologically confirmed rare liver tumors in 8 patients. All of the patients underwent ultrasound (US) guided biopsy and subsequent thermal ablation. The tumors were ablated according to the preoperative plans and monitored by real-time US. CT/MRI fused with contrast enhanced US (CEUS) or three-dimensional (3D) US-CEUS images were used to guide and assess the ablation zone more accurately during thermal ablation. The rate of technical efficacy was assessed based on the contrast-enhance CT/MRI (CECT/MRI) results one month after ablation. Local tumor progression (LTP), recurrence and complications were followed up and recorded. RESULTS: Among these twelve nodules, nine were subject to US-guided thermal ablation, whereas the other three inconspicuous nodules were subject to CEUS-guided thermal ablation. Intra-procedure CT/MRI-CEUS or 3D US-CEUS fusion imaging assessments demonstrated that the ablation zone sufficiently covered the original tumor, and no immediate supplementary ablation was required. Additionally, no major complications were observed during the follow-up period. The postoperative CECT/MRI confirmed that the technique success rate was 100%. Within the surveillance period of 13 months, no LTP or recurrence was noted. CONCLUSIONS: US-guided thermal ablation was feasible and safe for rare liver tumors. The use of fusion imaging technique might make US-guided thermal ablation as effective as surgical resection, and this technique might serve as a potential therapeutic modality for rare liver tumors in the future.

Intracavitary Contrast-Enhanced Ultrasound in the Management of Post-Surgical Gastrointestinal Fistulas.

The goal of this study was to investigate intracavitary contrast-enhanced ultrasound (IC-CEUS) measures in the management of post-surgical gastrointestinal (GI) fistula throughout detection, treatment and follow-up. From June 2010 to August 2016, patients who were administered ultrasound contrast agent (UCA) via a drainage tube for IC-CEUS were enrolled and retrospectively analyzed. They were suspected of having GI anastomotic fistulas or had been found to have fluid collections with ultrasound that were accompanied by abdominal pain or fever after surgical procedures. Forty-two patients met the inclusion criteria and were enrolled into this study. Twenty-two were confirmed to have GI fistulas confirmed by standard references. None were detected by conventional ultrasound. Although IC-CEUS successfully detected GI fistulas in 16 patients, it missed GI fistulas in 6 patients. One patient was misdiagnosed with a GI fistula. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the diagnosis of GI fistulas by IC-CEUS were 72.7% (16/22), 95.0% (19/20), 94.1% (16/17), 76.0% (19/25) and 83.3% (35/42), respectively. Twenty peritoneal fluid collections in 14 patients were related to fistulas by IC-CEUS based on the distribution of ultrasound contrast agents. Additional drainage was performed in 14 fistula-related fluid collections. Eight GI fistulas were judged to be cured after IC-CEUS re-evaluation, and the drainage tubes were removed from these patients. In conclusion, IC-CEUS can greatly improve the ability to diagnose post-surgical GI fistulas and may also play an important role in interventional treatment and follow-up.

Immediate evaluation and guidance of liver cancer thermal ablation by three-dimensional ultrasound/contrast-enhanced ultrasound fusion imaging.

PURPOSE: To investigate the feasibility and value of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US-CEUS) fusion imaging for the immediate evaluation of technical success and the guidance of supplementary ablation during the liver cancer thermal ablation procedure. MATERIALS AND METHODS: Patients diagnosed with malignant liver cancer intending to receive thermal ablation including radiofrequency ablation (RFA) or microwave ablation (MWA) were enrolled. 3D US-CEUS fusion imaging was used to immediately assess the technical success and guide supplementary ablation. Contrast-enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) was performed one month after ablation to assess the technique effectiveness of the ablation. The registration success rate, duration time of 3D US-CEUS fusion imaging, technique effectiveness rate and major complications were recorded. RESULTS: In total, 76 patients with 95 tumours who underwent RFA or MWA and assessed by 3D US-CEUS fusion imaging were enrolled. The registration success rate of 3D US-CEUS fusion imaging was 93.7% (89/95), and the duration time was 4.0 ± 1.1 min. Thirty lesions received supplementary ablation immediately during the procedure. The technique effectiveness rate of the ablation was 98.8% (81/82). There were no major complications related to ablation. CONCLUSIONS: 3D US-CEUS fusion imaging is a feasible and valuable technique for the immediate evaluation and guidance of supplementary ablation during the liver cancer thermal ablation procedure.