4.6 Article

Development of Functional Thyroid C Cell-like Cells from Human Pluripotent Cells in 2D and in 3D Scaffolds

Journal

CELLS
Volume 10, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/cells10112897

Keywords

pluripotent stem cells; endoderm; disease modelling; thyroid C cells

Categories

Funding

  1. NHMRC [1069757, 1050692]
  2. Stem Cells Australia SCA [2013F-9]
  3. Australian Research Council [FT130100514]
  4. University of Melbourne
  5. Murdoch Children's Research Institute, MCRI
  6. IPRS through the Department of Paediatrics, University of Melbourne
  7. APA (Int) PhD Scholarship through the Department of Paediatrics, University of Melbourne
  8. National Health and Medical Research Council of Australia [1069757] Funding Source: NHMRC
  9. Australian Research Council [FT130100514] Funding Source: Australian Research Council

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This study successfully differentiated human embryonic stem cells into thyroid C cell-like cells, mimicking the process of medullary thyroid carcinoma in vitro, providing a valuable platform for drug screening.
Medullary thyroid carcinoma contributes to about 3-4% of thyroid cancers and affects C cells rather than follicular cells. Thyroid C cell differentiation from human pluripotent stem cells has not been reported. We report the stepwise differentiation of human embryonic stem cells into thyroid C cell-like cells through definitive endoderm and anterior foregut endoderm and ultimobranchial body-like intermediates in monolayer and 3D Matrigel culture conditions. The protocol involved sequential treatment with interferon/transferrin/selenium/pyruvate, foetal bovine serum, and activin A, then IGF-1 (Insulin-like growth factor 1), on the basis of embryonic thyroid developmental sequence. As well as expressing C cell lineage relative to follicular-lineage markers by qPCR (quantitative polymerase chain reaction) and immunolabelling, these cells by ELISA (enzyme-linked immunoassay) exhibited functional properties in vitro of calcitonin storage and release of calcitonin on calcium challenge. This method will contribute to developmental studies of the human thyroid gland and facilitate in vitro modelling of medullary thyroid carcinoma and provide a valuable platform for drug screening.

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