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Cited by 367Pancreatic function and diabetesTissue Engineering and Regenerative MedicineDiabetes Management and Research

Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques

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Bochenek, Matthew A., Veiseh, Omid, Vegas, Arturo J., McGarrigle, James J., Qi, Meirigeng, Marchese, Enza, Omami, Mustafa, Doloff, Joshua C. +22 more·2018·Nature Biomedical Engineering
DOI 10.1038/s41551-018-0275-1PMC PMC6413527
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Abstract

The transplantation of pancreatic islet cells could restore glycaemic control in patients with type-I diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in diabetic rodent models; yet human patients transplanted with equivalent microsphere formulations have experienced only transient islet-graft function, owing to a vigorous foreign-body reaction (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing, in non-human primate (NHP) models, of seven alginate formulations that were efficacious in rodents, including three that led to transient islet-graft function in clinical trials. Although one month post-implantation all formulations elicited significant FBR and PFO, three chemically modified, immune-modulating alginate formulations elicited reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.

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  • The triazole-thiomorpholine dioxide alginate formulation was subsequently shown to prevent fibrosis and facilitate cell survival of allogeneic islets in non-human primates.

    “This formulation was subsequently shown to prevent fibrosis and facilitate cell survival of allogeneic islets in non-human primates.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [105]

    The Methods section identifies Z1-Y15 as a triazole–thiomorpholine dioxide modification. The paper reports viable allogeneic islets in non-human primates and no pericapsular fibrotic overgrowth in six of seven animals after transplantation. That supports reduced fibrosis and islet survival, but not the unqualified claim that the formulation prevented fibrosis. (LLM, conf=0.86)

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Authors
Bochenek, M. A., Veiseh, O., Vegas, A. J., McGarrigle, J. J., Qi, M., Marchese, E., Omami, M., Doloff, J. C., Mendoza-Elias, J., Nourmohammadzadeh, M., Khan, A., Yeh, C.-C., Xing, Y., Isa, D., Ghani, S., Li, J., Landry, C., Bader, A. R., Olejnik, K., Chen, M., Hollister-Lock, J., Wang, Y., Greiner, D. L., Weir, G. C., Strand, B. L., Rokstad, A. M. A., Lacik, I., Langer, R., Anderson, D. G., & Oberholzer, J.
Affiliations
  • Boston Children's Hospital (US)
  • Boston University (US)
  • University of Illinois Chicago (US)
  • North Carolina State University (US)
  • University of Massachusetts Chan Medical School (US)
  • Joslin Diabetes Center (US)
  • Norwegian University of Science and Technology (NO)
Corresponding author
Anderson, Daniel G.
ORCID
Venue
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Published
2018-08-13
Volume
2
Issue
11
Pages
810-821
ISSN
2157-846X (ISSN-L)
DOI
10.1038/s41551-018-0275-1
PMC
PMC6413527
OpenAlex
W2885954000
Cited by
367
References
68
Citations by year
2026: 37 · 2025: 46 · 2024: 50 · 2023: 47 · 2022: 43 · 2021: 64 · 2020: 47 · 2019: 31 · 2018: 2
FWCI
37.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Biomedical Engineering (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • PMC
Funders
  • U.S. Department of Defense (W81XWH, W81XWH1310215, W81XWH-13)
  • Leona M. and Harry B. Helmsley Charitable Trust
  • Agentúra na Podporu Výskumu a Vývoja (APVV-14-858)
  • Università degli Studi di Perugia
  • National Institutes of Health (4r37eb000244-34, W81XWH, 1uc4dk104218-01, CA151884, EB-000244, UC4-DK104218)
  • University of Illinois at Urbana-Champaign
  • National Cancer Institute (U54CA151884)
  • National Institute of Diabetes and Digestive and Kidney Diseases (UC4-DK-104218, R01DK091526, P30DK036836)
  • National Institute of Biomedical Imaging and Bioengineering (R01EB000244, R37-EB000244, R01EB000351)
  • National Institute of Dental and Craniofacial Research (R01DE013023)
  • Congressionally Directed Medical Research Programs
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
alginate encapsulation, islet transplantation, type 1 diabetes, foreign body reaction, immunoprotection, omental bursa, nonhuman primate model, allogeneic islets, insulin deficiency

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