Abstract
In the current clinical islet transplantation, intraportal transplantation is regarded as the gold-standard procedure. However, in this procedure, 50 to 70% of the transplanted islets are immediately damaged due to a strong innate immune response based on islet–blood contact. We investigated the transplant efficiency of a novel method of liver surface transplantation using a syngeneic keratinocyte sheet to avoid islet–blood contact. To examine the influence of the keratinocyte sheet, substantial amounts of syngeneic islets (8 IEQs/g) were transplanted on the liver surface of diabetic rats, while marginal amounts of islets (4 IEQs/g) were transplanted via intraportal transplantation to compare the transplant efficiency. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, and in vivo imaging findings of the cell sheet were evaluated. The study showed that islet transplantation to the liver surface immediately followed by a syngeneic keratinocyte sheet covering was effective for curing diabetic rats, while no rats were cured in the group without the cell sheet. Notably, islet grafts transplanted via this approach appeared to penetrate into the liver parenchyma. However, the transplant efficiency did not reach that of intraportal transplantation. Further refinements of this approach by introducing mesothelial or fibroblast cell sheets in combination with a preferable scaffold for islet grafts may help to improve the transplant efficiency.
Highlights
Pancreatic islet transplantation has become an established treatment for severe type 1 diabetic patients [1,2,3]
intravenous glucose tolerance test (IVGTT) Results The glucose tolerance was significantly ameliorated in the cell sheet group compared with the control group (Figure 4A–C)
Immunohistochemical Staining of the Transplanted Islets and Keratinocyte Sheets on the Liver Surface
Summary
Pancreatic islet transplantation has become an established treatment for severe type 1 diabetic patients [1,2,3]. Intraportal islet injection is regarded as an established procedure for clinical islet transplantation. This method has several drawbacks, including the risk of portal vein embolism [4] and the occurrence of strong innate immune reactions [5]. After intraportal islet transplantation 50 to 70% of islet grafts are immediately destroyed due to the instant blood-mediated inflammatory reaction (IBMIR) characterized by the activation of both coagulation and complement cascades [6,7,8,9]. Interrupting islet–blood contact to avoid IBMIR may be one way to improve engraftment efficiency in intraportal islet transplantation. The development of approaches involving islet transplantation to a new site wherein islet–blood contact can be avoided is eagerly anticipated
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