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

Abstract

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.

Adipose‐Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold

“…[93] A tissue engineered biomaterial based scaffold that is transplantable to an extrahepatic site and also easily retrievable, would give an invaluable knowledge and a possibility to monitor long-term islet function toward investigation of alternative and novel regenerative approaches for T1D treatment. [94][95][96] In this study, we used our defined minimal mass of islets together with ASCs, to study the indirect effects of ASCs in the scaffolds. ≥200 mouse islets are considered a full islet mass that is required to achieve normoglycemia in allogenic diabetic mouse model.…”

Comparison of Omentum and Subcutis as Implant Sites for Device-Encapsulated Human iPSC-Derived Pancreatic Endoderm in Nude Rats

“…Implants are accessible for safely taking biopsies, and being outside a vital organ, can be completely resected when needed for safety. These considerations have led to investigating this site for non-encapsulated islet cell implants in animal models and in clinical pilot studies 9 , 11 , 12 , 32 – 34 . Clinical studies demonstrated the technical feasibility of implantations and explantations, and its perspective for analyzing composition of implants and their microenvironment.…”

“…These preparations were shown to engraft in the OM depending on their composition and scaffold 9 , 10 . Functional outcome in patients has been marginal in our center 10 and the university of Alberta 11 , but one case of insulin-independence has been reported by the university of Miami 12 ; the centers in Alberta and Miami have now joint a clinical trial with the same study protocol (NCT02821026).…”

Impact of Prevascularization on Immunological Environment and Early Engraftment in Subcutaneous Islet Transplantation

“… 3 , 4 However, the necessary islet cells are difficult to secure because of donor shortage; the transplanted cells may also be damaged because of the activation of the complement and blood coagulation systems and innate immune response during intrahepatic portal vein transplantation, 5 , 6 which remains the gold standard for clinical islet transplantation. 7 Donor shortage might be solved by utilizing islet-like cells derived from embryonic stem cells–induced pluripotent stem cells. In this case, the subcutaneous region is a promising transplantation site because it enables graft observation and removal, thereby ensuring safety, and the transplantation of a large number of cells without adverse effects associated with intraportal transplantation using minimally invasive methods.…”