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Cited by 106Pancreatic function and diabetesTissue Engineering and Regenerative MedicineDiabetes and associated disorders

Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

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Nalbach, Lisa, Roma, Leticia P, Schmitt, Beate M, Becker, Vivien, Körbel, Christina, Wrublewsky, Selina, Pack, Mandy, Später, Thomas +10 more·2021·EMBO Molecular Medicine
DOI 10.15252/emmm.202012616PMC PMC7799357
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Abstract

Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin‐secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non‐prevascularized islet organoids. This is caused by paracrine signaling between the β‐cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo , the prevascularized islet organoids are rapidly blood‐perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation.

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  • Islets embedded within sub-millimeter collagen cylinders coated with endothelial cells or combined with microvascular fragments became rapidly vascularized and connected to the host vasculature when transplanted into rodents.

    “Alternatively, islets embedded within sub-millimeter collagen cylinders coated with endothelial cells154 or islets combined with microvascular fragments155 were demonstrated to become rapidly vascularized and connected to the host vasculature when transplanted into rodents.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [155]

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Authors
Nalbach, L., Roma, L. P., Schmitt, B. M., Becker, V., Körbel, C., Wrublewsky, S., Pack, M., Später, T., Metzger, W., Menger, M. M., Frueh, F. S., Götz, C., Lin, H., Manning Fox, J. E., MacDonald, P. E., Menger, M. D., Laschke, M. W., & Ampofo, E.
Affiliations
  • Saarland University (DE)
  • University of Tübingen (DE)
  • University of Zurich (CH)
  • University of Alberta (CA)
Corresponding author
Ampofo, Emmanuel
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2020-11-02
Volume
13
Issue
1
Pages
e12616-e12616
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
DOI
10.15252/emmm.202012616
PMC
PMC7799357
OpenAlex
W3096335179
Cited by
106
References
71
Citations by year
2026: 8 · 2025: 20 · 2024: 27 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 1
FWCI
11.63
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Publications of the UdS (Saarland University) (cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Prof. Dr. Theiss‐Forschungspreis
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
islet transplantation, type 1 diabetes, angiogenesis, paracrine signaling, pancreatic beta cells, endothelial cells, insulin receptor, islet engraftment, islet grafts, normoglycemia
MeSH terms
Animals, Diabetes Mellitus, Experimental, Insulin, Islets of Langerhans, Islets of Langerhans Transplantation, Endothelial Cells, Insulin-Secreting Cells, Mice

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