Sulfated Alginate Reduces Pericapsular Fibrotic Overgrowth on Encapsulated CGMP-Compliant HPSC-Hepatocytes in Mice

Overview

Journal Front Bioeng Biotechnol

Date 2022 Mar 21

PMID 35308825

Authors

Adam M Syanda

Vera I Kringstad

Samuel J I Blackford

Joachim S Kjesbu

Soon Seng Ng

Liang Ma

Fang Xiao

Abba E Coron

Anne Mari A Rokstad

Sunil Modi

S Tamir Rashid

Berit Lokensgard Strand

Affiliations

Soon will be listed here.

Abstract

Intra-peritoneal placement of alginate encapsulated human induced pluripotent stem cell-derived hepatocytes (hPSC-Heps) represents a potential new bridging therapy for acute liver failure. One of the rate-limiting steps that needs to be overcome to make such a procedure more efficacious and safer is to reduce the accumulation of fibrotic tissue around the encapsulated cells to allow the free passage of relevant molecules in and out for metabolism. Novel chemical compositions of alginate afford the possibility of achieving this aim. We accordingly used sulfated alginate and demonstrated that this material reduced fibrotic overgrowth whilst not impeding the process of encapsulation nor cell function. Cumulatively, this suggests sulfated alginate could be a more suitable material to encapsulate hPSC-hepatocyte prior to human use.

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References

Dhawan A, Chaijitraruch N, Fitzpatrick E, Bansal S, Filippi C, Lehec S . Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children. J Hepatol. 2019; 72(5):877-884. DOI: 10.1016/j.jhep.2019.12.002. View

Weiler J, Yurt R, Fearon D, Austen K . Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. J Exp Med. 1978; 147(2):409-21. PMC: 2184494. DOI: 10.1084/jem.147.2.409. View

Arlov O, Ozturk E, Steinwachs M, Skjak-Braek G, Zenobi-Wong M . Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes. Eur Cell Mater. 2017; 33:76-89. DOI: 10.22203/eCM.v033a06. View

Park H, Kim J, Lee S, Yang H, Ham D, Sun C . Antifibrotic effect of rapamycin containing polyethylene glycol-coated alginate microcapsule in islet xenotransplantation. J Tissue Eng Regen Med. 2015; 11(4):1274-1284. DOI: 10.1002/term.2029. View

Coron A, Kjesbu J, Kjaernsmo F, Oberholzer J, Rokstad A, Strand B . Pericapsular fibrotic overgrowth mitigated in immunocompetent mice through microbead formulations based on sulfated or intermediate G alginates. Acta Biomater. 2021; 137:172-185. DOI: 10.1016/j.actbio.2021.10.004. View

Vaithilingam V, Kollarikova G, Qi M, Larsson R, Lacik I, Formo K . Beneficial effects of coating alginate microcapsules with macromolecular heparin conjugates-in vitro and in vivo study. Tissue Eng Part A. 2013; 20(1-2):324-34. DOI: 10.1089/ten.TEA.2013.0254. View

Arlov O, Aachmann F, Sundan A, Espevik T, Skjak-Braek G . Heparin-like properties of sulfated alginates with defined sequences and sulfation degrees. Biomacromolecules. 2014; 15(7):2744-50. DOI: 10.1021/bm500602w. View

Jacobs-Tulleneers-Thevissen D, Chintinne M, Ling Z, Gillard P, Schoonjans L, Delvaux G . 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):1605-14. DOI: 10.1007/s00125-013-2906-0. View

Mei J, Sgroi A, Mai G, Baertschiger R, Gonelle-Gispert C, Serre-Beinier V . Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. Cell Transplant. 2009; 18(1):101-10. DOI: 10.3727/096368909788237168. View

10.

Bunger C, Tiefenbach B, Jahnke A, Gerlach C, Freier T, Schmitz K . Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids. Biomaterials. 2004; 26(15):2353-60. DOI: 10.1016/j.biomaterials.2004.07.017. View

11.

Tuch B, Keogh G, Williams L, Wu W, Foster J, Vaithilingam V . Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care. 2009; 32(10):1887-9. PMC: 2752920. DOI: 10.2337/dc09-0744. View

12.

Chen T, Yuan J, Duncanson S, Hibert M, Kodish B, Mylavaganam G . Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression. Am J Transplant. 2015; 15(3):618-27. DOI: 10.1111/ajt.13049. View

13.

King A, Lau J, Nordin A, Sandler S, Andersson A . The effect of capsule composition in the reversal of hyperglycemia in diabetic mice transplanted with microencapsulated allogeneic islets. Diabetes Technol Ther. 2003; 5(4):653-63. DOI: 10.1089/152091503322250677. View

14.

Ricci M, Blasi P, Giovagnoli S, Rossi C, Macchiarulo G, Luca G . Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation. J Control Release. 2005; 107(3):395-407. DOI: 10.1016/j.jconrel.2005.06.023. View

15.

Calafiore R, Basta G, Luca G, Lemmi A, Montanucci M, Calabrese G . Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care. 2005; 29(1):137-8. DOI: 10.2337/diacare.29.1.137. View

16.

Asrani S, Devarbhavi H, Eaton J, Kamath P . Burden of liver diseases in the world. J Hepatol. 2018; 70(1):151-171. DOI: 10.1016/j.jhep.2018.09.014. View

17.

Jitraruch S, Dhawan A, Hughes R, Filippi C, Soong D, Philippeos C . Alginate microencapsulated hepatocytes optimised for transplantation in acute liver failure. PLoS One. 2014; 9(12):e113609. PMC: 4249959. DOI: 10.1371/journal.pone.0113609. View

18.

Bohm F, Kohler U, Speicher T, Werner S . Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med. 2010; 2(8):294-305. PMC: 3377328. DOI: 10.1002/emmm.201000085. View

19.

Bernal W, Cross T, Auzinger G, Sizer E, Heneghan M, Bowles M . Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience. J Hepatol. 2008; 50(2):306-13. DOI: 10.1016/j.jhep.2008.09.012. View

20.

Chen X, Shao W, Chen J, Zhang L, Matthias C, Shan S . Allotransplantation of sulphate glucomannan-alginate barium (SGA)-microencapsulated rat islets for the treatment of diabetes mellitus. Immunol Invest. 2009; 38(7):561-71. DOI: 10.1080/08820130902984828. View