Status of Islet Transplantation and Innovations to Sustainable Outcomes: Novel Sites, Cell Sources, and Drug Delivery Strategies

Overview

Journal Front Transplant

Specialty General Surgery

Date 2024 Nov 18

PMID 39553396

Authors

Jordan M Wong

Andrew R Pepper

Affiliations

Soon will be listed here.

Abstract

Islet transplantation (ITx) is an effective means to restore physiologic glycemic regulation in those living with type 1 diabetes; however, there are a handful of barriers that prevent the broad application of this functionally curative procedure. The restricted cell supply, requisite for life-long toxic immunosuppression, and significant immediate and gradual graft attrition limits the procedure to only those living with brittle diabetes. While intraportal ITx is the primary clinical site, portal vein-specific factors including low oxygen tension and the instant blood-mediated inflammatory reaction are detrimental to initial engraftment and long-term function. These factors among others prevent the procedure from granting recipients long-term insulin independence. Herein, we provide an overview of the status and limitations of ITx, and novel innovations that address the shortcomings presented. Despite the marked progress highlighted in the review from as early as the initial islet tissue transplantation in 1893, ongoing efforts to improve the procedure efficacy and success are also explored. Progress in identifying unlimited cell sources, more favourable transplant sites, and novel drug delivery strategies all work to broaden ITx application and reduce adverse outcomes. Exploring combination of these approaches may uncover synergies that can further advance the field of ITx in providing sustainable functional cures. Finally, the potential of biomaterial strategies to facilitate immune evasion and local immune modulation are featured and may underpin successful application in alternative transplant sites.

References

de Jong W, Borm P . Drug delivery and nanoparticles:applications and hazards. Int J Nanomedicine. 2008; 3(2):133-49. PMC: 2527668. DOI: 10.2147/ijn.s596. View

Tuch B, Madrid J, Summers E, Smith M . Production and characterization of fetal sheep pancreatic islet-like cell clusters. Cell Transplant. 1996; 5(4):491-8. DOI: 10.1177/096368979600500408. View

Kondo Y, Toyoda T, Inagaki N, Osafune K . iPSC technology-based regenerative therapy for diabetes. J Diabetes Investig. 2017; 9(2):234-243. PMC: 5835458. DOI: 10.1111/jdi.12702. View

DAmour K, Bang A, Eliazer S, Kelly O, Agulnick A, Smart N . Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006; 24(11):1392-401. DOI: 10.1038/nbt1259. View

Wu J, Li T, Guo M, Ji J, Meng X, Fu T . Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue. Cell Discov. 2024; 10(1):45. PMC: 11058776. DOI: 10.1038/s41421-024-00662-3. View

Wang L, Ernst A, Flanders J, Liu W, Wang X, Datta A . An inverse-breathing encapsulation system for cell delivery. Sci Adv. 2021; 7(20). PMC: 8121434. DOI: 10.1126/sciadv.abd5835. View

OGorman D, Kin T, Murdoch T, Richer B, McGhee-Wilson D, Ryan E . The standardization of pancreatic donors for islet isolations. Transplantation. 2005; 80(6):801-6. DOI: 10.1097/01.tp.0000172216.47547.d5. View

Piemonti L, Pileggi A . 25 YEARS OF THE RICORDI AUTOMATED METHOD FOR ISLET ISOLATION. CellR4 Repair Replace Regen Reprogram. 2018; 1(1). PMC: 6267808. View

Matsumoto S, Tan P, Baker J, Durbin K, Tomiya M, Azuma K . Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant Proc. 2014; 46(6):1992-5. DOI: 10.1016/j.transproceed.2014.06.008. View

10.

Hogrebe N, Ishahak M, Millman J . Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell. 2023; 30(5):530-548. PMC: 10167558. DOI: 10.1016/j.stem.2023.04.002. View

11.

Woehrle M, Markmann J, Silvers W, Barker C, Naji A . Transplantation of cultured pancreatic islets to BB rats. Surgery. 1986; 100(2):334-41. View

12.

Johansson H, Goto M, Dufrane D, Siegbahn A, Elgue G, Gianello P . Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation. Am J Transplant. 2006; 6(2):305-12. DOI: 10.1111/j.1600-6143.2005.01186.x. View

13.

Luo H, Duguid W, Chen H, Maheu M, Wu J . The effect of rapamycin on T cell development in mice. Eur J Immunol. 1994; 24(3):692-701. DOI: 10.1002/eji.1830240331. View

14.

Atkinson M, Eisenbarth G, Michels A . Type 1 diabetes. Lancet. 2013; 383(9911):69-82. PMC: 4380133. DOI: 10.1016/S0140-6736(13)60591-7. View

15.

Giuliani M, Moritz W, Bodmer E, Dindo D, Kugelmeier P, Lehmann R . Central necrosis in isolated hypoxic human pancreatic islets: evidence for postisolation ischemia. Cell Transplant. 2005; 14(1):67-76. DOI: 10.3727/000000005783983287. View

16.

Dimitrioglou N, Kanelli M, Papageorgiou E, Karatzas T, Hatziavramidis D . Paving the way for successful islet encapsulation. Drug Discov Today. 2019; 24(3):737-748. DOI: 10.1016/j.drudis.2019.01.020. View

17.

Nishimura R, Goto M, Sekiguchi S, Fujimori K, Ushiyama A, Satomi S . Assessment for revascularization of transplanted pancreatic islets at subcutaneous site in mice with a highly sensitive imaging system. Transplant Proc. 2011; 43(9):3239-40. DOI: 10.1016/j.transproceed.2011.09.095. View

18.

LAUBE F, BLECH W, Schroder D, Besch W, Hildebrandt W, Hahn H . The action of cyclosporin A on the endocrine pancreas in vitro--functional and morphological studies. Exp Clin Endocrinol. 1986; 87(1):69-78. DOI: 10.1055/s-0029-1210525. View

19.

Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R . Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002; 360(9350):2039-45. DOI: 10.1016/s0140-6736(02)12020-4. View

20.

Herold K, Lancki D, Moldwin R, Fitch F . Immunosuppressive effects of cyclosporin A on cloned T cells. J Immunol. 1986; 136(4):1315-21. View