Biodegradable biliary stents coated with mesenchymal stromal cells in a porcine choledochojejunostomy model.

BACKGROUND AIMS: Roux en y anastomosis is a preferred method of biliary reconstruction in liver transplantation that involves living donors or pediatric patients. However, biliary stricture is a frequent and serious complication, accounting for up to 40% of biliary complications in these patients. Previously, we demonstrated that extraluminal delivery of adipose-derived (AD) mesenchymal stromal cells (MSCs) decreased peri-biliary fibrosis and increased neo-angiogenesis in a porcine model of duct-to-duct biliary anastomosis. In this study, we used a porcine model of Roux en y anastomosis to evaluate the beneficial impact of a novel intraluminal MSC delivery system. METHODS: Nine animals were divided into three groups: no stent (group 1), bare stent (group 2) and stent coated with AD-MSCs (group 3). All animals underwent cholecystectomy with roux en y choledochojejunostomy. Two animals per group were followed for 4 weeks and one animal per group was followed for 8 weeks. Cholangiograms and blood were sampled at baseline and the end of study. Biliary tissue was collected and examined by Masson trichrome staining and immunohistochemical staining for MSC markers (CD34 and CD44) and for neo-angiogenesis (CD31). RESULTS: Two of three animals in group 1 developed an anastomotic site stricture. No strictures were observed in the animals of group 2 or group 3. CD34 and CD44 staining showed that AD-MSCs engrafted successfully at the anastomotic site by intraluminal delivery (group 3). Furthermore, biliary tissue from group 3 showed significantly less fibrosis and increased angiogenesis compared with the other groups. CONCLUSIONS: Intraluminal delivery of AD-MSCs resulted in successful biliary engraftment of AD-MSCs as well as reduced peri-biliary fibrosis and increased neo-angiogenesis.

Does preoperative embolization improve outcomes of meningioma resection? A systematic review and meta-analysis.

Current evidence regarding the benefit of preoperative embolization (POE) of meningiomas is inconclusive. This systematic review and meta-analysis aims to evaluate the safety profile of the procedure and to compare outcomes in embolized versus non-embolized meningiomas. PubMed was queried for studies after January 1990 reporting outcomes of POE. Pertinent variables were extracted and synthesized from eligible articles. Heterogeneity was assessed using I2, and random-effects model was employed to calculate pooled 95% CI effect sizes. Publication bias was assessed using funnel plots and Harbord's and Begg's tests. Meta-analyses were used to assess estimated blood loss and operative duration (mean difference; MD), gross-total resection (odds ratio; OR), and postsurgical complications and postsurgical mortality (risk difference; RD). Thirty-four studies encompassing 1782 preoperatively embolized meningiomas were captured. The pooled immediate complication rate following embolization was 4.3% (34 studies, n = 1782). Although heterogeneity was moderate to high (I2 = 35-86%), meta-analyses showed no statistically significant differences in estimated blood loss (8 studies, n = 1050, MD = 13.9 cc, 95% CI = -101.3 to 129.1), operative duration (11 studies, n = 1887, MD = 2.4 min, 95% CI = -35.5 to 30.8), gross-total resection (6 studies, n = 1608, OR = 1.07, 95% CI = 0.8-1.5), postsurgical complications (12 studies, n = 2060, RD = 0.01, 95% CI = -0.04 to 0.07), and postsurgical mortality (12 studies, n = 2060, RD = 0.01, 95% CI = 0-0.01). Although POE is relatively safe, no clear benefit was observed in operative and postoperative outcomes. However, results must be interpreted with caution due to heterogeneity and selection bias between studies. Well-controlled future investigations are needed to define the patient population most likely to benefit from the procedure.

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC-seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin-eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose-derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.