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Surface Coating of Pancreatic Islets With Neural Crest Stem Cells Improves Engraftment and Function After Intraportal Transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
2015 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 24, no 11, 2263-2272 p.Article in journal (Refereed) Published
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Abstract [en]

The present study aimed to develop techniques for surface coating of islets with neural crest stem cells (NCSCs) in order to enable cotransplantation to the clinically used liver site and then investigate engraftment and function intraportally of such bioengineered islets. Mouse islets were coated during incubation with enhanced green fluorescent protein (EGFP)-expressing mouse NCSCs and transplanted into the portal vein to cure diabetic mice. An intravenous glucose tolerance test was performed at 1 month posttransplantation. Islet grafts were retrieved and evaluated for vascular density, nerves, and glial cells. NCSCs expressed a vast number of key angiogenic and neurotrophic factors. Mice transplanted with NCSC-bioengineered islets responded better to the glucose load than recipient mice with control islets. NCSCs remained present in the vicinity or had often migrated into the NCSC-coated islets, and an improved islet graft reinnervation and revascularization was observed. Transplanted NCSCs differentiated into both glial and neural cells in the islet grafts. We conclude that bioengineering of islets with NCSCs for intraportal transplantation provides a possibility to improve islet engraftment and function. Pending successful establishment of protocols for expansion of NCSCs from, for example, human skin or bone marrow, this strategy may be applied to clinical islet transplantation.

Place, publisher, year, edition, pages
2015. Vol. 24, no 11, 2263-2272 p.
Keyword [en]
Islet transplantation, Stem cells, Neural progenitors, Engraftment, Revascularization, Reinnervation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-269293DOI: 10.3727/096368915X686184ISI: 000364353300008PubMedID: 25581301OAI: oai:DiVA.org:uu-269293DiVA: diva2:882614
Funder
Swedish Research Council, 20716Swedish Research Council, 55X-15043Novo NordiskSwedish Diabetes AssociationSwedish Child Diabetes FoundationNovo NordiskAFA InsuranceSwedish Society of MedicineMagnus Bergvall Foundation
Available from: 2015-12-15 Created: 2015-12-15 Last updated: 2017-12-01Bibliographically approved

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Lau Börjesson, JoeyVasylovska, SvitlanaKozlova, Elena N.Carlsson, Per-Ola
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Department of Medical Cell BiologyClinical diabetology and metabolismDepartment of NeuroscienceTransplantation and regenerative medicine
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Cell Transplantation
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cell Biology

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