title: Transdifferentiation of Bone Marrow Mesenchymal Stem Cells into the Islet-Like Cells: the Role of Extracellular Matrix Proteins.
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.
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland. marta.pokrywczynska@interia.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Pokrywczynska
authors.affiliation: Department of Molecular Oncology and Genetics, Innovative Medical Forum, Franciszek Łukaszczyk Oncology Center, Bydgoszcz, Poland.|Department of Thoracic Surgery and Tumors, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Marzena Anna
authors.initials: MA
authors.lastname: Lewandowska
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Krzyzanowska
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Jundzill
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Rasmus
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Warda
authors.affiliation: Department of Histology and Embryology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Gagat
authors.affiliation: Department of Microbiology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Deptula
authors.affiliation: Department of Immunology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Helmin-Basa
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznań, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Holysz
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Nowacki
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Buchholz
authors.affiliation: Department of Clinical Pathomorphology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Department of Clinical Pathomorphology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.|Department of Pathology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
authors.affiliation: Department of Histology and Embryology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Grzanka
authors.affiliation: Department of Tumor Pathology and Pathomorphology, Franciszek Łukaszczyk Oncology Center, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jozwicki
authors.affiliation: Department of Immunology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Michalkiewicz
authors.affiliation: Chair of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Toruń, Karlowicza 24, 85-092, Bydgoszcz, Poland.|Department of Urology, Nicolaus Copernicus Hospital, Toruń, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Drewa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D007797:Laminin / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome; D019096:Vitronectin / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D007328:Insulin; D007797:Laminin; D019096:Vitronectin; C121346:laminin 1
keywords: Collagen; Islet-like cells; Laminin; Mesenchymal stem cells; Transdifferentiation; Vitronectin