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

Alexandra M Smink; Samuel Rodriquez; Shiri Li; Bryan Ceballos; Nicole Corrales; Michael Alexander; Taco Koster; Bart J de Haan; Jonathan R T Lakey; Paul de Vos

doi:10.1097/TXD.0000000000001417

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

Transplant Direct. 2022 Dec 22;9(1):e1417. doi: 10.1097/TXD.0000000000001417. eCollection 2023 Jan.

Authors

Alexandra M Smink^{1

2}, Samuel Rodriquez², Shiri Li^{2

3}, Bryan Ceballos², Nicole Corrales², Michael Alexander², Taco Koster¹, Bart J de Haan¹, Jonathan R T Lakey^{2

4}, Paul de Vos¹

Affiliations

¹ Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
² Department of Surgery, University of California Irvine, Orange, CA.
³ Department of Surgery, New York Presbyterian Hospital, Weill Cornell College of Medicine, New York, NY.
⁴ Department of Biomedical Engineering, University of California Irvine, Irvine, CA.

Abstract

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.