Causes of limited survival of microencapsulated pancreatic islet grafts

de Groot, Martijn; Schuurs, Theo A.; van Schilfgaarde, Reinout

doi:10.1016/j.jss.2004.02.018

Cited by 170Pancreatic function and diabetesTissue Engineering and Regenerative MedicineDiabetes Management and Research

Causes of limited survival of microencapsulated pancreatic islet grafts

de Groot, Martijn, Schuurs, Theo A., van Schilfgaarde, Reinout·2004·Journal of Surgical Research

DOI 10.1016/j.jss.2004.02.018

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Abstract

Successful transplantation of pancreatic tissue has been demonstrated to be an efficacious method of restoring glycemic control in type 1 diabetic patients. To establish graft acceptance patients require lifelong immunosuppression, which in turn is associated with severe deleterious side effects. Microencapsulation is a technique that enables the transplantation of pancreatic islets in the absence of immunosuppression by protecting the islet tissue through a mechanical barrier. This protection may even allow for the transplantation of animal tissue, which opens the perspective of using animal donors as a means to solve the problem of organ shortage. Microencapsulation is not yet applied in clinical practice, mainly because encapsulated islet graft survival is limited. In the present review we discuss the principal causes of microencapsulated islet graft failure, which are related to a lack of biocompatibility, limited immunoprotective properties, and hypoxia. Next to the causes of encapsulated islet graft failure we discuss possible improvements in the encapsulation technique and additional methods that could prolong encapsulated islet graft survival. Strategies that may well support encapsulated islet grafts include co-encapsulation of islets with Sertoli cells, the genetic modification of islet cells, the creation of an artificial implantation site, and the use of alternative donor sources. We conclude that encapsulation in combination with one or more of these additional strategies may well lead to a simple and safe transplantation therapy as a cure for diabetes.

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Prior work by the authors and others showed that cellular and collagen deposition on the surface of transplanted 0.5 mm alginate microcapsules causes encapsulated islet graft death and failure to correct diabetes in STZ-treated C57BL/6 mice.
“Previously, we and others have shown that host recognition and fibrosis via cellular and collagen deposition on the surface of transplanted 0.5 mm sized alginate microcapsules results in encapsulated islet graft cell death and the failure of diabetic correction in STZ-treated C57BL/6 mice28, 37, 38.”
From Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015) · cites this paper as [38]

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Authors: de Groot, M., Schuurs, T. A., & van Schilfgaarde, R.
Affiliations: University Medical Center Groningen (NL)
Venue: Journal of Surgical Research
Publisher: Elsevier BV
Published: 2004-09
Volume: 121
Issue: 1
Pages: 141-150
ISSN: 0022-4804 (ISSN-L)
DOI: 10.1016/j.jss.2004.02.018
OpenAlex: W2116348979
Cited by: 170
References: 101
Citations by year: 2025: 2 · 2024: 2 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 11 · 2012: 11
FWCI: 1.83
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Surgical Research (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords: microencapsulation, islet transplantation, type 1 diabetes, islet graft survival, graft failure, biocompatibility, immunoprotection, hypoxia, Sertoli cells, xenotransplantation, immunosuppression-free transplantation
MeSH terms: Alginates, Graft Survival, Humans, Polylysine, Cell Hypoxia, Islets of Langerhans Transplantation

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Causes of limited survival of microencapsulated pancreatic islet grafts

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