Engineering Vascularized Islet Macroencapsulation Devices: An Platform to Study Oxygen Transport in Perfused Immobilized Pancreatic Beta Cell Cultures

Overview

Journal Front Bioeng Biotechnol

Date 2022 May 6

PMID 35519615

Authors

Fernandez S A

Champion K S

Danielczak L

Gasparrini M

Paraskevas S

Leask R L

Hoesli C A

Affiliations

Soon will be listed here.

Abstract

Islet encapsulation devices serve to deliver pancreatic beta cells to type 1 diabetic patients without the need for chronic immunosuppression. However, clinical translation is hampered by mass transport limitations causing graft hypoxia. This is exacerbated in devices relying only on passive diffusion for oxygenation. Here, we describe the application of a cylindrical perfusion system to study oxygen effects on islet-like clusters immobilized in alginate hydrogel. Mouse insulinoma 6 islet-like clusters were generated using microwell plates and characterized with respect to size distribution, viability, and oxygen consumption rate to determine an appropriate seeding density for perfusion studies. Immobilized clusters were perfused through a central channel at different oxygen tensions. Analysis of histological staining indicated the distribution of viable clusters was severely limited to near the perfusion channel at low oxygen tensions, while the distribution was broadest at normoxia. The results agreed with a 3D computational model designed to simulate the oxygen distribution within the perfusion device. Further simulations were generated to predict device performance with human islets under and conditions. The combination of experimental and computational findings suggest that a multichannel perfusion strategy could support viability and function of a therapeutic islet dose.

Citing Articles

Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization.

Moeun B, Lemaire F, Smink A, Ebrahimi Orimi H, Leask R, de Vos P J Tissue Eng. 2025; 16:20417314241284826.

PMID: 39866963 PMC: 11758540. DOI: 10.1177/20417314241284826.

Islet cell spheroids produced by a thermally sensitive scaffold: a new diabetes treatment.

Yao X, Gong Z, Yin W, Li H, Douroumis D, Huang L J Nanobiotechnology. 2024; 22(1):657.

PMID: 39456025 PMC: 11515210. DOI: 10.1186/s12951-024-02891-w.

Hypoxia within subcutaneously implanted macroencapsulation devices limits the viability and functionality of densely loaded islets.

Einstein S, Steyn L, Weegman B, Suszynski T, Sambanis A, OBrien T Front Transplant. 2024; 2:1257029.

PMID: 38993891 PMC: 11235299. DOI: 10.3389/frtra.2023.1257029.

In vitro oxygen imaging of acellular and cell-loaded beta cell replacement devices.

Kotecha M, Wang L, Hameed S, Viswakarma N, Ma M, Stabler C Sci Rep. 2023; 13(1):15641.

PMID: 37730815 PMC: 10511476. DOI: 10.1038/s41598-023-42099-w.

Long-term cultures of human pancreatic islets in self-assembling peptides hydrogels.

Marchini A, Ciulla M, Antonioli B, Agnoli A, Bovio U, Visnoviz V Front Bioeng Biotechnol. 2023; 11:1105157.

PMID: 36911193 PMC: 9995881. DOI: 10.3389/fbioe.2023.1105157.

References

Papas K, Long Jr R, Constantinidis I, Sambanis A . Effects of oxygen on metabolic and secretory activities of beta TC3 cells. Biochim Biophys Acta. 1996; 1291(2):163-6. DOI: 10.1016/0304-4165(96)00062-1. View

Albro M, Chahine N, Caligaris M, Wei V, Likhitpanichkul M, Ng K . Osmotic loading of spherical gels: a biomimetic study of hindered transport in the cell protoplasm. J Biomech Eng. 2007; 129(4):503-10. PMC: 2828939. DOI: 10.1115/1.2746371. View

Buder B, Alexander M, Krishnan R, Chapman D, Lakey J . Encapsulated islet transplantation: strategies and clinical trials. Immune Netw. 2014; 13(6):235-9. PMC: 3875781. DOI: 10.4110/in.2013.13.6.235. View

Cristea D, Krishtul S, Kuppusamy P, Baruch L, Machluf M, Blank A . New approach to measuring oxygen diffusion and consumption in encapsulated living cells, based on electron spin resonance microscopy. Acta Biomater. 2019; 101:384-394. DOI: 10.1016/j.actbio.2019.10.032. View

Buchwald P . A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets. Theor Biol Med Model. 2011; 8:20. PMC: 3138450. DOI: 10.1186/1742-4682-8-20. View

Olsson R, Carlsson P . Oxygenation of cultured pancreatic islets. Adv Exp Med Biol. 2006; 578:263-8. DOI: 10.1007/0-387-29540-2_42. View

Avgoustiniatos E, Colton C . Effect of external oxygen mass transfer resistances on viability of immunoisolated tissue. Ann N Y Acad Sci. 1998; 831:145-67. DOI: 10.1111/j.1749-6632.1997.tb52192.x. View

Hoesli C, Luu M, Piret J . A novel alginate hollow fiber bioreactor process for cellular therapy applications. Biotechnol Prog. 2009; 25(6):1740-51. DOI: 10.1002/btpr.260. View

Fernandez S, Danielczak L, Gauvin-Rossignol G, Hasilo C, Begin-Drolet A, Ruel J . An Perfused Macroencapsulation Device to Study Hemocompatibility and Survival of Islet-Like Cell Clusters. Front Bioeng Biotechnol. 2021; 9:674125. PMC: 8193939. DOI: 10.3389/fbioe.2021.674125. View

10.

Hoesli C, Raghuram K, Kiang R, Mocinecova D, Hu X, Johnson J . Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation. Biotechnol Bioeng. 2010; 108(2):424-34. DOI: 10.1002/bit.22959. View

11.

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

12.

Komatsu H, Cook C, Gonzalez N, Medrano L, Salgado M, Sui F . Oxygen transporter for the hypoxic transplantation site. Biofabrication. 2018; 11(1):015011. PMC: 9851375. DOI: 10.1088/1758-5090/aaf2f0. View

13.

Jones G, Juszczak M, Hughes S, Kooner P, Powis S, Press M . Time course and quantification of pancreatic islet revascularization following intraportal transplantation. Cell Transplant. 2007; 16(5):505-16. DOI: 10.3727/000000007783464993. View

14.

Dionne K, Colton C, Yarmush M . Effect of hypoxia on insulin secretion by isolated rat and canine islets of Langerhans. Diabetes. 1993; 42(1):12-21. DOI: 10.2337/diab.42.1.12. View

15.

Magisson J, Sassi A, Xhema D, Kobalyan A, Gianello P, Mourer B . Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model. J Tissue Eng. 2020; 11:2041731420924818. PMC: 7257875. DOI: 10.1177/2041731420924818. View

16.

Suszynski T, Avgoustiniatos E, Papas K . Intraportal islet oxygenation. J Diabetes Sci Technol. 2014; 8(3):575-80. PMC: 4455447. DOI: 10.1177/1932296814525827. View

17.

Liljeback H, Grapensparr L, Olerud J, Carlsson P . Extensive Loss of Islet Mass Beyond the First Day After Intraportal Human Islet Transplantation in a Mouse Model. Cell Transplant. 2015; 25(3):481-9. DOI: 10.3727/096368915X688902. View

18.

Mehmetoglu U, Ates S, Berber R . Oxygen diffusivity in calcium alginate gel beads containing Gluconobacter suboxydans. Artif Cells Blood Substit Immobil Biotechnol. 1996; 24(2):91-106. DOI: 10.3109/10731199609118877. View

19.

Lehmann R, Zuellig R, Kugelmeier P, Baenninger P, Moritz W, Perren A . Superiority of small islets in human islet transplantation. Diabetes. 2007; 56(3):594-603. DOI: 10.2337/db06-0779. View

20.

Cao R, Avgoustiniatos E, Papas K, de Vos P, Lakey J . Mathematical predictions of oxygen availability in micro- and macro-encapsulated human and porcine pancreatic islets. J Biomed Mater Res B Appl Biomater. 2019; 108(2):343-352. DOI: 10.1002/jbm.b.34393. View