The Optimal Maturation of Subcutaneous Pouch Can Improve Pancreatic Islets Engraftment in Rat Model

Abstract

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.

Successful Islet Transplantation Into a Subcutaneous Polycaprolactone Scaffold in Mice and Pigs

“…This leads to improved nutrient delivery and less loss of islet cells due to hypoxia and necrosis. Furthermore, it supports the glycemic control of the grafted islets in the scaffold, as also shown with a similar approach by Patikova et al 34 A possible disadvantage is the need for 2 separate surgical procedures. However, these are simple procedures that might even be done under local anesthesia.…”

Emerging strategies for beta cell transplantation to treat diabetes

“…Distribution in the vicryl mesh prevented islet aggregation and promoted vascular infiltration. Patikova et al created a vascularized SQ space by implanting a microporous polyamide scaffold combined with a Teflon bar insert [65]. Interestingly, they found that a 5-day healing period after removal of the Teflon bar on day 7 (day 7 + 5) increased vascular density, whereas Teflon removal on day 28 resulted in rapid vessel regression.…”

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

“…Implantation of nylon catheters or cylindrical stainless-steel mesh tubing in rodents helped to create vascularized pouches in 1 month, exploiting the foreign body response (FBR) without inducing scar formation in different tissues. After removal, syngeneic islets or human islets were easily implanted, showing the ability to reverse diabetes in the respective appropriate rodent models (84), while islets infused in the not-preconditioned pouch were not able to restore normoglycemia (85)(86)(87)(88)(89). Similarly, poly-D,L-lactide-co-εcaprolactone (PLCL)-based scaffolds were used to prevascularize the subcutaneous space after 1 month.…”