We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

The effectiveness of cell transplantation can be improved by optimization of the transplantation site.

A.P. performed the majority of surgical experiments and participated in data analysis and writing of the article. A.V. processed all samples for histological analysis, performed immunohistological and immunofluorescence staining, and participated in writing of the article. E.F. participated in research design and performed some surgical experiments. L.K. participated in islet isolation, cultivation, and transplantation and participated in writing of the article. A.H. participated in Original Basic Science Background. Transplantation of pancreatic islets into subcutaneous cavities in diabetic rats may be as or even more effective than transplantation into the portal vein. Identifying the optimal timing of the individual steps in this procedure is critical. Methods. Macroporous scaffolds were placed in the subcutaneous tissue of diabetic male Lewis rats for 7 or 28 d and the healing of the tissue inside the scaffolds was monitored. A marginal syngeneic graft comprising 4 islets/g of recipient body weight was transplanted at the best timing focusing mainly on vascularization. Recipients were monitored for blood glucose levels and tolerance tests. Histological examination was performed in all implanted scaffolds. The presence of individual endocrine cells was analyzed in detail. Results. Blood glucose levels remained within the physiological range in all recipients until the end of experiment as well as body weight increase. Coefficients of glucose assimilation were normal or slightly reduced with no statistically significant differences between the groups 40 and 80 d after transplantation. Histological analysis revealed round viable islets in the liver similar to those in pancreas, but alpha cells practically disappeared, whereas islets in the scaffolds formed clusters of cells surrounded by rich vascular network and the alpha cells remained partially preserved. Conclusions. Subcutaneous transplantation of pancreatic islets is considerably less invasive but comparably efficient as commonly used islet transplantation into the portal vein. In consideration of alpha and beta cell ratio, the artificial subcutaneous cavities represent a promising site for future islet transplantation therapy. (Transplantation 2022;106: 531-542). morphological analysis of pouch and islet samples and participated in writing of the article. E.S. participated in study design preparation and writing of the article. Z.B. participated in islet isolation, cultivation, and transplantation; tissue samples collecting; and writing of the article. Z.H. participated in surgical experiments and islet transplantation. J.K. prepared the design of the study and participated in the performance of the research, data analysis, and the writing of the article.

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