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.
Similar content being viewed by others
References
Bonner-Weir S, Taneja M, Weir GC et al (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 97:7999–8004
Boyd AS, Wu DC, Higashi Y et al (2008) A comparison of protocols used to generate insulin-producing cell clusters from mouse embryonic stem cells. Stem Cells 26:1128–1137
Chang CF, Hsu KH, Chiou SH et al (2008) Fibronectin and pellet suspension culture promote differentiation of human mesenchymal stem cells into insulin producing cells. J Biomed Mater Res A 86:1097–1105
Cirulli V, Beattie GM, Klier G et al (2000) Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells. J Cell Biol 150:1445–1460
Ende N, Chen R, Reddi AS (2004a) Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice. Biochem Biophys Res Commun 325:665–669
Ende N, Chen R, Reddi AS (2004b) Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice. Biochem Biophys Res Commun 321:168–171
Hisanaga E, Park KY, Yamada S et al (2008) A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4. Endocr J 55:535–543
Hori Y, Gu X, Xie X et al (2005) Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2:e103
Hulinsky I, Harrington J, Cooney S et al (1995) Insulin secretion and DNA synthesis of cultured islets of Langerhans are influenced by the matrix. Pancreas 11:309–314
Lin HY, Tsai CC, Chen LL et al (2010) Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK. J Biomed Sci 17:56
Moriscot C, de Fraipont F, Richard MJ (2005) Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 23:594–603
Pepper AR, Gala-Lopez B, Ziff O et al (2013) Current status of clinical islet transplantation. World J Transplant 3:48–53
Pokrywczynska M, Jundzill A, Bodnar M et al (2013a) Do mesenchymal stem cells modulate the milieu of reconstructed bladder wall? Arch Immunol Ther Exp 61:483–493
Pokrywczynska M, Krzyzanowska S, Jundzill A et al (2013b) Differentiation of stem cells into insulin-producing cells: current status and challenges. Arch Immunol Ther Exp 61:149–158
Ramiya VK, Maraist M, Arfors KE et al (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6:278–282
Schwitzgebel VM, Scheel DW, Conners JR et al (2000) Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 127:3533–3542
Shimoyama S, Gansauge F, Gansauge S et al (1995) Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas. Int J Pancreatol 18:227–234
Tateishi K, He J, Taranova O et al (2008) Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283:31601–31607
Van Deijnen JH, Van Suylichem PT, Wolters GH et al (1994) Distribution of collagens type I, type III and type V in the pancreas of rat, dog, pig and man. Cell Tissue Res 277:115–121
Yang L, Li S, Hatch H et al (2002) In vitro trans differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA 99:8078–8083
Zhang Y, Shen W, Hua J et al (2010) Pancreatic islet-like clusters from bone marrow mesenchymal stem cells of human first-trimester abortus can cure streptozocin-induced mouse diabetes. Rejuvenation Res 13:695–706
Acknowledgments
This work was supported by Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Faculty of Medicine, Young Scientist Grant MN-12/WL.
Conflict of interest
The authors declare no potential conflict of interest.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Pokrywczynska, M., Lewandowska, M.A., Krzyzanowska, S. et al. Transdifferentiation of Bone Marrow Mesenchymal Stem Cells into the Islet-Like Cells: the Role of Extracellular Matrix Proteins. Arch. Immunol. Ther. Exp. 63, 377–384 (2015). https://doi.org/10.1007/s00005-015-0340-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00005-015-0340-3