Transplantation of Pancreatic Islets Into the Omentum Using a Biocompatible Plasma-Thrombin Gel: First Experience at the Institute for Clinical and Experimental Medicine in Prague

Saudek, F; Hladíková, Zuzana; Hagerf, Barbora; Nemétová, Lenka; Girman, Peter; Kříž, Jan; Marada, Tomáš; Hui‐Kang, David; Berková, Zuzana; Leontovyč, Ivan; Froněk, Jiří

doi:10.1016/j.transproceed.2021.11.037

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…35 Two recent studies evaluating omental ITx in humans have found similar results to ours, with >50% of patients having early graft failure, and others achieving marginal clinical benefit. 36,37 Of note, the Van Hulle et al 36 group evaluated graft biopsies and demonstrated that substantial foreign body reaction may have led to their outcomes. Similarly, our results contrast with promising findings of allotransplantation of porcine islets within the gastric submucosa in immunosuppressed pigs reported by Echeverri et al 10 Importantly, the gross and microscopic gastric anatomy differs between humans and porcine models, with the porcine stomach being 2-3 times larger and having much more cardiac mucosa than humans.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study

et al. 2022

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Background. Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. Methods. This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. Results. Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1–3 mo post–first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. Conclusions. Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study

et al. 2022

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“…Transplanting islets into the liver has several notorious limitations that could be potentially overcome by placing the islet graft into alternative, extrahepatic locations. Among the alternatives, the greater omentum has shown promise, both experimentally [ 2 , 23 ] and in human pilot trials [ 24 , 25 ]. The advantages of the omentum include its high vascularization, its easy surgical accessibility, and its large surface area, which allows transplantation of larger and less purified or encapsulated islet grafts and the possibility of graft retrieval, when needed [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…This approach could provide a rich vascular supply but would avoid direct contact with the blood [ 21 ]. Experimental data [ 2 , 22 , 23 ] and first clinical experiences [ 24 , 25 ] have suggested that this approach has potential, but to date, it has not replaced hepatic placement. Therefore, we reasoned that pancreatic ECM skeletons, with accurate microstructure and biochemical composition, might provide an optimal tissue-specific environment for isolated islets.…”

Section: Introductionmentioning

confidence: 99%

Decellularized Pancreatic Tail as Matrix for Pancreatic Islet Transplantation into the Greater Omentum in Rats

Berková

Zacharovová

Patikova

et al. 2022

JFB

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Infusing pancreatic islets into the portal vein currently represents the preferred approach for islet transplantation, despite considerable loss of islet mass almost immediately after implantation. Therefore, approaches that obviate direct intravascular placement are urgently needed. A promising candidate for extrahepatic placement is the omentum. We aimed to develop an extracellular matrix skeleton from the native pancreas that could provide a microenvironment for islet survival in an omental flap. To that end, we compared different decellularization approaches, including perfusion through the pancreatic duct, gastric artery, portal vein, and a novel method through the splenic vein. Decellularized skeletons were compared for size, residual DNA content, protein composition, histology, electron microscopy, and MR imaging after repopulation with isolated islets. Compared to the other approaches, pancreatic perfusion via the splenic vein provided smaller extracellular matrix skeletons, which facilitated transplantation into the omentum, without compromising other requirements, such as the complete depletion of cellular components and the preservation of pancreatic extracellular proteins. Repeated MR imaging of iron-oxide-labeled pancreatic islets showed that islets maintained their position in vivo for 49 days. Advanced environmental scanning electron microscopy demonstrated that islets remained integrated with the pancreatic skeleton. This novel approach represents a proof-of-concept for long-term transplantation experiments.

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“…At present, pedicled omental ap, as a source of biomaterials, has been widely used in the prevention or treatment of complications, such as rectovaginal stula and vesicovaginal stula, cerebrovascular reconstruction, tissue damage repair, and as a carrier to promote regeneration, etc. [49][50][51][52] , which has solved many clinical treatment problems. The pedicled omentum was free and transplanted to the pelvic oor to simulate the reconstruction of the mesentery around the neorectum and the presacral tissue, which avoided the intestinal stiffness caused by the adhesion between the neo-rectum and the presacral tissue, reduced the pressure of the neo-rectum, improved the compliance of the neo-rectum, and increased the defecation buffer.…”

Section: Discussionmentioning

confidence: 99%

Mesorectal reconstruction with pedicled greater omental transplantation to relieve low anterior resection syndrome following total intersphincteric resection in patients with ultra-low rectal cancer

Liao

Qin

Wang

et al. 2022

Preprint

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BACKGROUND AND OBJECTIVES: Total intersphincteric resection (ISR) is the ultimate anus-preserving surgery for patients with ultra-low rectal cancer (ULRC), which can result in various degrees of anorectal dysfunction. Known as low anterior resection syndrome (LARS), it seriously affects the postoperative quality of life of patients. The aim of this study was to discuss the value of mesorectal reconstruction with pedicled greater omental transplantation (PGOT) to relieve LARS following total ISR in patients with ULRC, hoping to provide new ideas and strategies for the prevention and improvement of LARS. METHODS We retrospectively analyzed hospitalization data and postoperative anorectal function of 26 ULRC patients, who were met inclusion and exclusion criteria in our center from January 2015 to February 2022. And combined with the results of anorectal manometry and rectal magnetic resonance imaging (MRI) defecography of some patients, we assessed comprehensively anorectal physiological and morphological changes of the patients after surgery, and their correlation with LARS. RESULTS In this study, 26 patients with ULRC were enrolled and divided into observation group (n = 15) and control group (n = 11) according to whether pedicled omental transplantation was performed. There were no significant differences in surgical results such as operative time, intraoperative blood loss and postoperative complications between the two groups (P > 0.05). Postoperative follow-up showed that patients in both groups showed severe LARS within 3 months after surgery, but from the 3rd month after surgery, LARS in both groups gradually began to decrease, especially in the observation group, which showed faster recovery and better recovery, with statistically significant differences (P < 0.001). Through anorectal manometry, the mean rectal resting pressure in the observation group was significantly lower than that in the control group (P = 0.010). In addition, the postoperative thickness of the posterior rectal mesenterium in the observation group was significantly higher than that in the control group (P = 0.001), and also higher than the preoperative level (P = 0.018). Moreover, rectal MRI defecography showed that the new rectum had good compliance under the matting of greater omentum, and its intestinal peristalsis was coordinated. CONCLUSION ULRC patients, with the help of greater omentum, coordinated their neo-rectum peristalsis after total ISR and recovery of LARS was faster and better. PGOT is expected to be an effective strategy for LARS prevention and treatment of ULRC patients after surgery and is worthy of clinical promotion.

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Transplantation of Pancreatic Islets Into the Omentum Using a Biocompatible Plasma-Thrombin Gel: First Experience at the Institute for Clinical and Experimental Medicine in Prague

Cited by 10 publications

References 17 publications

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study

Decellularized Pancreatic Tail as Matrix for Pancreatic Islet Transplantation into the Greater Omentum in Rats

Mesorectal reconstruction with pedicled greater omental transplantation to relieve low anterior resection syndrome following total intersphincteric resection in patients with ultra-low rectal cancer

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