Surface Coating of Pancreatic Islets With Neural Crest Stem Cells Improves Engraftment and Function After Intraportal Transplantation
2015 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 24, no 11, 2263-2272 p.Article in journal (Refereed) PublishedText
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.
Islet transplantation, Stem cells, Neural progenitors, Engraftment, Revascularization, Reinnervation
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-269293DOI: 10.3727/096368915X686184ISI: 000364353300008PubMedID: 25581301OAI: oai:DiVA.org:uu-269293DiVA: diva2:882614
FunderSwedish Research Council, 20716Swedish Research Council, 55X-15043Novo NordiskSwedish Diabetes AssociationSwedish Child Diabetes FoundationNovo NordiskAFA InsuranceSwedish Society of MedicineMagnus Bergvall Foundation