RRC ID 18612
Author Kasuda S, Tatsumi K, Sakurai Y, Kato J, Taminishi S, Takeda T, Ohashi K, Okano T, Hatake K, Shima M.
Title Expression of coagulation factors from murine induced pluripotent stem cell-derived liver cells.
Journal Blood Coagul. Fibrinolysis
Abstract A protocol to differentiate liver cells from induced pluripotent stem (iPS) cells is being established. However, the ability of these differentiated iPS cells to express liver-specific proteins, such as coagulation cascade and related factors, has yet to be assessed. This study evaluated whether liver-like populations differentiated from murine iPS cells gain the ability to produce coagulation-related factors. Following differentiation of murine iPS cells into hematopoietic-like and liver-like embryoid bodies, we assessed gene expression profiles for coagulation-related markers, including fibrinogen, factors II, V, VII, VIII, IX, X, XI, XII, and XIIIβ, protein C, protein S, antithrombin, plasminogen, von Willebrand factor, and ADAMTS13 by real-time reverse transcription PCR. Liver-like embryoid bodies demonstrated strong expression levels of nearly all the coagulation-related genes assessed, compared with undifferentiated iPS cells and hematopoietic-like embryoid bodies. We also confirmed efficient translation and secretion of fibrinogen and albumin (hepatocyte-specific marker proteins) into the conditioned medium by these differentiated cells, suggesting successful differentiation of iPS cells into the liver lineage. These findings suggest that iPS cells can be differentiated into liver-like populations that express coagulation-related factors. Liver-like embryoid bodies may provide a source for cell-based therapies directed toward liver diseases, including coagulation factor deficiencies in the future.
Volume 22(4)
Pages 271-9
Published 2011-6
DOI 10.1097/MBC.0b013e328344c63b
PMID 21415711
MeSH ADAMTS13 Protein Animals Antithrombins / metabolism Biomarkers / analysis* Blood Coagulation Disorders / blood* Blood Coagulation Disorders / physiopathology Blood Coagulation Disorders / therapy Blood Coagulation Factors / genetics Blood Coagulation Factors / metabolism* Cell Culture Techniques Cell Differentiation Cell Line Embryoid Bodies / cytology Embryoid Bodies / metabolism* Female Gene Expression Hepatocytes / cytology Hepatocytes / metabolism* Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism* Liver / cytology Liver / metabolism* Metalloendopeptidases / genetics Metalloendopeptidases / metabolism Mice Mice, Inbred C57BL Molecular Targeted Therapy Protein C / genetics Protein C / metabolism Protein S / genetics Protein S / metabolism RNA, Messenger / analysis Stem Cell Transplantation
IF 1.12
Times Cited 5
Human and Animal Cells iPS-MEF-Ng-20D-17 (APS0001)