Transdifferentiation of Bone Marrow Mesenchymal Stem Cells into the Islet-Like Cells: the Role of Extracellular Matrix Proteins

Arch Immunol Ther Exp (Warsz). 2015 Oct;63(5):377-84. doi: 10.1007/s00005-015-0340-3. Epub 2015 May 10.

Abstract

Pancreatic islet implantation has been recently shown to be an efficient method of treatment for type 1 diabetes. However, limited availability of donor islets reduces its use. Bone morrow would provide potentially unlimited source of stem cells for generation of insulin-producing cells. This study was performed to evaluate the influence of extracellular matrix proteins like collagen, laminin, and vitronectin on bone marrow mesenchymal stem cells (BM-MSCs) transdifferentiation into islet-like cells (ILCs) in vitro. To our knowledge, this is the first report evaluating the importance of vitronectin in transdifferentiation of BM-MSCs into ILCs. Rat BM-MSCs were induced to ILCs using four-step protocol on plates coated with collagen type IV, laminin type I and vitronectin type I. Quantitative real-time PCR was performed to detect gene expression related to pancreatic β cell development. The induced cells expressed islet-related genes including: neurogenin 3, neurogenic differentiation 1, paired box 4, NK homeobox factor 6.1, glucagon, insulin 1 and insulin 2. Laminin but not collagen type IV or vitronectin enhanced expression of insulin and promoted formation of islet-like structures in monolayer culture. Laminin triggered transdifferentiation of BM-MSCs into ILCs.

Keywords: Collagen; Islet-like cells; Laminin; Mesenchymal stem cells; Transdifferentiation; Vitronectin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology*
  • Cell Transdifferentiation
  • Cells, Cultured
  • Collagen Type IV / metabolism
  • Diabetes Mellitus, Type 1 / therapy*
  • Extracellular Matrix / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans Transplantation*
  • Laminin / metabolism
  • Male
  • Mesenchymal Stem Cells / physiology*
  • Rats
  • Rats, Wistar
  • Transcriptome
  • Vitronectin / metabolism

Substances

  • Collagen Type IV
  • Insulin
  • Laminin
  • Vitronectin
  • laminin 1