Functional Thyroid Follicular cells Differentiation from human-induced Pluripotent stem cells in suspension culture

被引:15
作者
Arauchi, Ayumi [1 ]
Matsuura, Katsuhisa [1 ,2 ]
Shimizu, Tatsuya [1 ]
Okano, Teruo [1 ]
机构
[1] Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Tokyo, Japan
[2] Tokyo Womens Med Univ, Dept Cardiol, Tokyo, Japan
关键词
induced pluripotent stem cells; differentiation; 3D-cell culture; thyroid transcription factor; thyroid follicular cells; EFFICIENT DIFFERENTIATION; DEFINITIVE ENDODERM; HUMAN FIBROBLASTS; PAX8; EXPRESSION; GENERATION; GLAND; LUNG; TRANSPLANTATION; ORGANOGENESIS;
D O I
10.3389/fendo.2017.00103
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The replacement of regenerated thyroid follicular cells (TFCs) is a promising therapeutic strategy for patients with hypothyroidism. Here, we have succeeded in inducing functional TFCs from human-induced pluripotent stem cells (iPSCs) in scalable suspension culture. Differentiation of iPSCs with Activin A treatment produced Sox17- and FoxA2-expressing definitive endodermal cells that also expressed thyroid transcription factors Pax8 and Nkx2-1. Further treatment with thyroid-stimulating hormone (TSH) induced TFCs expressing various types of thyroid proteins including TSH receptor, sodium-iodide symporter, thyroglobulin, and thyroid peroxidase. Interestingly, differentiated cells secreted free thyroxine in vitro. These results indicate successful differentiation of human iPSCs to functional TFCs that may enable us to fabricate thyroid tissues for regenerative medicine and disease models.
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页数:11
相关论文
共 40 条
[1]   Generation of functional thyroid from embryonic stem cells [J].
Antonica, Francesco ;
Kasprzyk, Dominika Figini ;
Opitz, Robert ;
Iacovino, Michelina ;
Liao, Xiao-Hui ;
Dumitrescu, Alexandra Mihaela ;
Refetoff, Samuel ;
Peremans, Kathelijne ;
Manto, Mario ;
Kyba, Michael ;
Costagliola, Sabine .
NATURE, 2012, 491 (7422) :66-U170
[2]  
Arauchi A, 2009, TISSUE ENG PT A, V15, P3943, DOI [10.1089/ten.tea.2009.0119, 10.1089/ten.TEA.2009.0119]
[3]   Directed differentiation of mouse embryonic stem cells into thyroid follicular cells [J].
Arufe, Maria C. ;
Lu, Min ;
Kubo, Atsushi ;
Keller, Gordon ;
Davies, Terry F. ;
Lin, Reigh-Yi .
ENDOCRINOLOGY, 2006, 147 (06) :3007-3015
[4]   Differentiation of murine embryonic stern cells to thyrocytes requires insulin and indulin-like growth factor-1 [J].
Arufe, Maria C. ;
Lu, Min ;
Lin, Reigh-Yi .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 381 (02) :264-270
[5]  
Barbera JPM, 2000, DEVELOPMENT, V127, P2433
[6]   Efficient differentiation of human embryonic stem cells to definitive endoderm [J].
D'Amour, KA ;
Agulnick, AD ;
Eliazer, S ;
Kelly, OG ;
Kroon, E ;
Baetge, EE .
NATURE BIOTECHNOLOGY, 2005, 23 (12) :1534-1541
[7]   Thyroid Progenitors Are Robustly Derived from Embryonic Stem Cells through Transient, Developmental Stage-Specific Overexpression of Nkx2-1 [J].
Dame, Keri ;
Cincotta, Steven ;
Lang, Alex H. ;
Sanghrajka, Reeti M. ;
Zhang, Liye ;
Choi, Jinyoung ;
Kwok, Letty ;
Wilson, Talitha ;
Kandula, Maciej M. ;
Monti, Stefano ;
Hollenberg, Anthony N. ;
Mehta, Pankaj ;
Kotton, Darrell N. ;
Ikonomou, Laertis .
STEM CELL REPORTS, 2017, 8 (02) :216-225
[8]  
di Magliano MP, 2000, P NATL ACAD SCI USA, V97, P13144
[9]   Pax8 has a critical role in epithelial cell survival and proliferation [J].
Di Palma, T. ;
Filippone, M. G. ;
Pierantoni, G. M. ;
Fusco, A. ;
Soddu, S. ;
Zannini, M. .
CELL DEATH & DISEASE, 2013, 4 :e729-e729
[10]   RESTORATION OF THYROID-FUNCTION AFTER TOTAL THYROIDECTOMY AND QUANTITATIVE THYROID-CELL TRANSPLANTATION [J].
DOMANN, FE ;
MITCHEN, JM ;
CLIFTON, KH .
ENDOCRINOLOGY, 1990, 127 (06) :2673-2678