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

Abstract

Background. Islet transplantation is a promising treatment for type 1 diabetes. It has the potential to improve glycemic control, particularly in patients suffering from hypoglycemic unawareness and glycemic instability. As most islet grafts do not function permanently, efforts are needed to create an accessible and replaceable site, for islet grafts or for insulin-producing cells obtained from replenishable sources. To this end, we designed and tested an artificial, polymeric subcutaneous transplantation site that allows repeated transplantation of islets. Methods. In this study, we developed and compared scaffolds made of poly(D,L,-lactide-co-ε-caprolactone) (PDLLCL) and polycaprolactone (PCL). Efficacy was first tested in mice‚ and then, as a proof of principle for application in a large animal model, the scaffolds were tested in pigs, as their skin structure is similar to that of humans. Results. In mice, islet transplantation in a PCL scaffold expedited return to normoglycemia in comparison to PDLLCL (7.7 ± 3.7 versus 16.8 ± 6.5 d), but it took longer than the kidney capsule control group. PCL also supported porcine functional islet survival in vitro. Subcutaneous implantation of PDLLCL and PCL scaffolds in pigs revealed that PCL scaffolds were more stable and was associated with less infiltration by immune cells than PDLLCL scaffolds. Prevascularized PCL scaffolds were therefore used to demonstrate the functional survival of allogenic islets under the skin of pigs. Conclusions. To conclude, a novel PCL scaffold shows efficacy as a readily accessible and replaceable, subcutaneous transplantation site for islets in mice and demonstrated islet survival after a month in pigs.

Emerging Strategies for Beta Cell Encapsulation for Type 1 Diabetes Therapy

“…Additionally, PCL has been used as a vehicle for beta cell transplantation and showed great islet survival in both mice and pigs. [ 26 ] In 2022, Seyyedi et al. created an immunoprotective barrier for collagen macroencapsulated islets using PCL nanofibers.…”

“…Here they confirmed allogenic islet survival after one month. [ 26 ] Another example of large animal usage can be found by Wang and colleagues, who developed an immunoshielding nanofibrous encapsulation device. They first confirmed the safety and therapeutic effect in rodents before they explored and confirmed device scalability and retrievability in intraperitoneally in a dog.…”

“…Additionally, PCL has been used as a vehicle for beta cell transplantation and showed great islet survival in both mice and pigs. [26] In 2022, Seyyedi et al created an immunoprotective barrier for collagen macroencapsulated islets using PCL nanofibers. The fibrous shell was found to allow oxygen and nutrient transport, however, its immunoprotective function was not studied and confirmed in vivo.…”