Treatment of diabetes by transplantation of pancreatic islets and insulin-producing cells protected from the immune system by encapsulation

Czech version

Authors: Igor Lacík
Authors‘ workplace: Ústav polymérov SAV, v. v. i., Bratislava
Published in: Diab Obez 2024; 24(48): 112-119
Category: Reviews

Overview

It is now clear that cell therapy via transplantation of insulin-producing cells, i.e. primary pancreatic islets or reprogrammed stem cells, is an option for the treatment of type 1 diabetes mellitus (T1DM) in patients in whom the desired control of sugar levels cannot be achieved by insulin administration. The complications associated with long-term use of immunosuppressive drugs represent the key limitation of cell therapy. This limitation can be eliminated by encapsulating the cells in a semipermeable polymeric membrane that provides selective permeation of glucose, insulin, nutrients, and metabolites and prevents efficient permeation of the immune system. An intensive research has been ongoing in the world for the last 40 years to provide a clinical solution to glycemic control by cell therapy without the need for immunosuppressive drugs. The aim of this paper is to provide an overview of the current status of T1DM cell therapy with a focus on encapsulation technologies. This topic is being addressed by hundreds of centers around the world working on various aspects related to this therapy. The author of this paper is working in the field of polymeric microcapsules development for immune protection of transplanted pancreatic islets. This paper does not attempt to saturate the reader with references to the existing extensive literature, but to provide a summary with references mainly to recent articles from which the reader will be able to identify the necessary information in his/her area of interest.

Keywords:

Transplantation – cell therapy – pancreatic islets – β-cells derived from stem cell reprogramming – type 1 diabetes mellitus (T1DM) – encapsulation for immune protection of transplanted cells – immunosuppres-sion

Sources

Latres E, Finan DA, Greenstein JL et al. Navigating Two Roads to Glucose Normalization in Diabetes: Automated Insulin Delivery Devices and Cell Therapy. Cell Metab 2019; 29(3): 545–563. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cmet.2019.02.007>.

Bellin MD, Dunn TB. Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies. Diabetologia 2020; 63(10): 2049–2056. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–020–05184–7>.

Shapiro AM, Lakey JR, Ryan EA et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343(4): 230–238. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM200007273430401>.

Williams J, Jacus N, Kavalackal K et al. Over ten-year insulin independence following single allogeneic islet transplant without T-cell depleting antibody induction. Islets 2018; 10(4): 168–174. Dostupné z DOI: <http://dx.doi.org/10.1080/19382014.2018.1451281>.

Barton FB, Rickels MR, Alejandro R et al. Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 2012; 35(7): 1436–1445. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0063>.

Bretzel RG, Jahr H, Eckhard M et al. Islet cell transplantation today. Langenbecks Arch Surg 2007; 392(3): 239–253. Dostupné z DOI: <http://dx.doi.org/10.1007/s00423–007–0183–4>.

Marfil-Garza BA, Imes S, Verhoeff K et al. Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada. Lancet Diabetes Endocrinol 2022; 10(7): 519–532. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(21)00147–9>.

Stanley AK, Duncan K, Anderson D et al. Insulin independence following islet transplantation improves long-term metabolic outcomes. Diabet Med 2024; 41(2): e15257. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.15257>.

Markmann JF, Rickels MR, Eggerman TL et al. Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. Am J Transplant 2021; 21(4): 1477–1492. Dostupné z DOI: <http://dx.doi.org/10.1111/ajt.16174>.

Berney T, Andres A, Bellin MD et al. A Worldwide Survey of Activities and Practices in Clinical Islet of Langerhans Transplantation. Transpl Int 2022; 35: 10507. Dostupné z DOI: <http://dx.doi.org/10.3389/ti.2022.10507>.

Ricordi C, Japour A. Transplanting islet cells can fix brittle diabetes. Why isn’t it available in the U.S.? CellR4 Repair Replace Regen Reprogram 2019; 7:e2768. Dostupné z DOI: <http://dx.doi.org/10.32113/cellr4_201910_2768>.

Lantidra. Dostupné z WWW: <https://www.lantidra.com/>.

Naziruddin B, Iwahashi S, Kanak MA et al. Evidence for Instant Blood-Mediated Inflammatory Reaction in Clinical Autologous Islet Transplantation. Am J Transplant 2014; 14(2): 428–437. Dostupné z DOI: <http://dx.doi.org/10.1111/ajt.12558>.

Kioulaphides S, García AJ. Encapsulation and immune protection for type 1 diabetes cell therapy. Adv Drug Deliv Rev 2024; 207 (2024): 115205. Dostupné z DOI: <http://dx.doi.org/10.1016/j.addr.2024.115205>.

Liu SS, Shim S, Kudo Y et al. Encapsulated islet transplantation. Nat Rev Bioeng 2024. Dostupné z DOI: <http://dx.doi.org/10.1038/s44222–024–00238–6>.

Wang S, Du Y, Zhang B et al. Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. Cell 2024: S0092–8674(24)01022–5. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cell.2024.09.004>.

Liang Z, Sun D, Lu S et al. Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets. Nature Metabolism 2023; 5(1): 29–40. Dostupné z DOI: <http://dx.doi.org/10.1038/s42255–022–00713–7>.

Hu X, White K, Young C et al. Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate. Cell Stem Cell 2024; 31(3): 334–340.e5. Dostupné z DOI: <http://dx.doi.org/10.1016/j.stem.2024.02.001>.

Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science 1980; 210(4472): 908- 910. Dostupné z DOI: <http://dx.doi.org/10.1126/science.6776628>.

Soon-Shiong P, Heintz RE, Merideth N et al. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 1994; 343(8903): 950–951. Dostupné z DOI: <http://dx.doi.org/10.1016/s0140–6736(94)90067–1>.

Scharp DW, Marchetti P. Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution. Adv Drug Deliv Rev 2014; 67–68: 35–73. Dostupné z DOI: <http://dx.doi.org/10.1016/j.addr.2013.07.018>.

Stock AA, Gonzalez GC, Pete SI et al. Performance of islets of Langerhans conformally coated via an emulsion cross-linking method in diabetic rodents and nonhuman primates. Sci Adv 2022: 8(26) (2022): eabm3145. Dostupné z DOI: <http://dx.doi.org/10.1126/sciadv.abm3145>.

Teramura Y, Oommen OP, Olerud J et al. Microencapsulation of cells, including islets, within stable ultra-thin membranes of maleimide-conjugated PEG-lipid with multifunctional crosslinkers. Biomaterials 2013; 34(11): 2683–2693. Dostupné z DOI: <http://dx.doi.org/10.1016/j.biomaterials.2013.01.015>.

Lacík I. Current Status on Immunoprotection of Transplanted Islets: Focus on Islet Microencapsulation. Micro and Nanosystems 2013; 5(3): 168–176. Dostupné z DOI: <http://dx.doi.org/10.2174/1876402911305030004>.

Lacík I. Polymer Chemistry in Diabetes Treatment by Encapsulated Islets of Langerhans: Review to 2006. Australian Journal of Chemistry 2006; 59(8): 508–524. Dostupné z DOI: <https://doi.org/10.1071/CH06197>.

Shapiro AM, Thompson D, Donner TW et al. Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device. Cell Rep Med 2021; 2(12): 100466. Dostupné z DOI: <http://dx.doi.org/10.1016/j.xcrm.2021.100466>.

Tuch BE, Keogh GW, Williams LJ et al. Safety and Viability of Microencapsulated Human Islets Transplanted Into Diabetic Humans. Diabetes Care 2009; 32(10): 1887–1889. <http://dx.doi.org/10.2337/dc09–0744>.

Jacobs-Tulleneers-Thevissen D, Chintinne M, Ling Z et al. [Beta Cell Therapy Consortium EU-FP7]. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 2013; 56(7: 1605–1614. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–013–2906–0>.

Basta G, Montanucci P, Luca G et al. Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Diabetes Care 2011; 34(11): 2406–2409. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11–0731>.

Calafiore R, Basta G, Luca G et al. Standard technical procedures for microencapsulation of human islets for graft into nonimmunosuppressed patients with type 1 diabetes mellitus. Transplant Proc 2006; 38(4): 1156–1157. Dostupné z DOI: <http://dx.doi.org/10.1016/j.transproceed.2006.03.014>.

Matsumoto S, Abalovich A, Wechsler C et al. Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes. EBioMedicine 2016; 12: 255–262. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ebiom.2016.08.034>.

Matsumoto S, Abalovich A, Wynyard S et al. Patients’ opinions 10 years after receiving encapsulated porcine islet xenotransplantation without immunosuppression. Xenotransplantation 2023; 30(3): e12798. Dostupné z DOI: <http://dx.doi.org/10.1111/xen.12798>.

Bochenek MA, Veiseh O, Vegas AJ et al. Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques. Nat Biomed Eng 2018; 2(11): 810–821. Dostupné z DOI: <http://dx.doi.org/10.1038/s41551–018–0275–1>.

Veiseh O, Doloff JC, Ma M et al. Anderson, Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater 2015; 14(6): 643–651. Dostupné z DOI: <http://dx.doi.org/10.1038/nmat4290>.

Vegas AJ, Veiseh O, Doloff JC et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 2016; 34(3): 345–352. Dostupné z DOI: <http://dx.doi.org/10.1038/nbt.3462>.

Chicago Diabetes Project. Dostupné z WWW: <https://www.chicagodiabetesproject.org/>.

Dorchei F, Heydari A, Kroneková Z et al. Postmodification with Polycations Enhances Key Properties of Alginate-Based Multicomponent Microcapsules. Biomacromolecules 2024; 25(7): 4118–4138. Dostupné z DOI: <http://dx.doi.org/10.1021/acs.biomac.4c00222>.

Vertex Pharmaceuticals. Dostupné z WWW: https://clinicaltrials.vrtx.com/.

Ludwig B, Reichel A, Steffen A et al. Transplantation of human islets without immunosuppression. Proc Natl Acad Sci U S A 2013; 110(47): 19054–19058. Dostupné z DOI: <http://dx.doi.org/10.1073/pnas.1317561110>.

Rokstad AM, Lacik I, de Vos P et al. Advances in biocompatibility and physico-chemical characterization of microspheres for cell encapsulation. Adv Drug Deliv Rev 2014; 67–68: 111–130. Dostupné z DOI: <http://dx.doi.org/10.1016/j.addr.2013.07.010>.