Formation of Composite Endothelial Cell–Mesenchymal Stem Cell Islets

A Novel Approach to Promote Islet Revascularization

  1. Ulrika Johansson1,
  2. Ida Rasmusson1,
  3. Simone P. Niclou2,
  4. Naomi Forslund1,
  5. Linda Gustavsson1,
  6. Bo Nilsson1,
  7. Olle Korsgren1 and
  8. Peetra U. Magnusson1
  1. 1Division of Clinical Immunology, the Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
  2. 2Centre de Recherche Public-Santé, NorLux Neuro-Oncology Laboratory, Val Fleuri, Luxembourg, Luxembourg
  1. Corresponding author: Ulrika Johansson, ulrika.johansson{at}klinimm.uu.se

Abstract

OBJECTIVE—Mesenchymal stem cells (MSCs) contribute to endothelial cell (EC) migration by producing proteases, thereby paving the way into the tissues for ECs. MSCs were added to our previously described composite EC islets as a potential means to improve their capacity for islet angiogenesis.

RESEARCH DESIGN AND METHODS—Human islets were coated with primary human bone marrow–derived MSCs and dermal microvascular ECs. The capacity of ECs, with or without MSCs, to adhere to and grow into human islets was analyzed. The survival and functionality of these composite islets were evaluated in a dynamic perifusion assay, and their capacity for angiogenesis in vitro was assessed in a three-dimensional fibrin gel assay.

RESULTS—ECs proliferated after culture in MSC-conditioned medium, and MSCs improved the EC coverage threefold compared with EC islets alone. Islet survival in vitro and the functionality of the composite islets after culture were equal to those of control islets. The EC-MSC islets showed a twofold increase in total sprout formation compared with EC islets, and vascular sprouts emanating from the EC-MSC–islet surface showed migration of ECs into the islets and also into the surrounding matrix, either alone or in concert with MSCs.

CONCLUSIONS—EC proliferation, sprout formation, and ingrowth of ECs into the islets were enhanced by MSCs. The use of composite EC-MSC islets may have beneficial effects on revascularization and immune regulation. The technique presented allows for pretreatment of donor islets with recipient-derived ECs and MSCs as a means of improving islet engraftment.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 2 June 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    See accompanying commentary, p. 2269.

    • Accepted May 23, 2008.
    • Received July 15, 2007.
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  1. Diabetes vol. 57 no. 9 2393-2401
  1. All Versions of this Article:
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