An important step towards a prevascularized islet microencapsulation device: in vivo prevascularization by combination of mesenchymal stem cells on micropatterned membranes

Milou Groot Nibbelink*, Katarzyna Skrzypek, Lisanne Karbaat, Sanne Both, Jacqueline Plass, Bettie Klomphaar, Jere van Lente, Sieger Henke, Marcel Karperien, Dimitrios Stamatialis, Aart van Apeldoorn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Extrahepatic transplantation of islets of Langerhans could aid in better survival of islets after transplantation. When islets are transfused into the liver 60-70% of them are lost immediately after transplantation. An important factor for a successful extrahepatic transplantation is a well-vascularized tissue surrounding the implant. There are many strategies known for enhancing vessel formation such as adding cells with endothelial potential, the combination with angiogenic factors and / or applying surface topography at the exposed surface of the device. Previously we developed porous, micropatterned membranes which can be applied as a lid for an islet encapsulation device and we showed that the surface topography induces human umbilical vein endothelial cell (HUVEC) alignment and interconnection. This was achieved without the addition of hydrogels, often used in angiogenesis assays. In this work, we went one step further towards clinical implementation of the device by combining this micropatterned lid with Mesenchymal Stem Cells (MSCs) to facilitate prevascularization in vivo. As for HUVECs, the micropatterned membranes induced MSC alignment and organization in vitro, an important contributor to vessel formation, whereas in vivo (subcutaneous rat model) they contributed to improved implant prevascularization. In fact, the combination of MSCs seeded on the micropatterned membrane induced the highest vessel formation score in 80% of the sections.

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Original languageEnglish
Article number174
Number of pages10
JournalJournal of Materials Science-Materials in Medicine
Volume29
Issue number11
DOIs
Publication statusPublished - 9 Nov 2018

Keywords

  • EXTRACELLULAR-MATRIX PROTEINS
  • DEPENDENT DIABETES-MELLITUS
  • ENDOTHELIAL GROWTH-FACTOR
  • BIOARTIFICIAL PANCREAS
  • ENCAPSULATED ISLETS
  • ENDOCRINE PANCREAS
  • GRAFT FUNCTION
  • STROMAL CELLS
  • TRANSPLANTATION
  • DIFFERENTIATION
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Membranes, Artificial
  • Mesenchymal Stem Cells
  • Tissue Scaffolds
  • Islets of Langerhans/blood supply
  • Drug Compounding
  • Neovascularization, Physiologic

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