4.3 Article

Seven diverse human embryonic stem cell-derived chondrogenic clonal embryonic progenitor cell lines display site-specific cell fates

Journal

REGENERATIVE MEDICINE
Volume 8, Issue 2, Pages 125-144

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/RME.12.117

Keywords

bone; cartilage; CD74; clonal embryonic progenitor cell; embryonic stem cell; HAND2; LHX1; LHX8; mesenchymal stem cell; osteoarthritis; PITX1; TBX15; ZIC2

Funding

  1. BioTime, Inc. (CA, USA)
  2. OrthoCyte Corp. (CA, USA)
  3. California Institute for Regenerative Medicine

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Aim: The transcriptomes of seven diverse clonal human embryonic progenitor cell lines with chondrogenic potential were compared with that of bone marrow-derived mesenchymal stem cells (MSCs). Materials & methods: The cell lines 4D20.8, 7PEND24, 7SMOO32, E15, MEL2, SK11 and SM30 were compared with MSCs using immunohistochemical methods, gene expression microarrays and quantitative real-time PCR. Results: In the undifferentiated progenitor state, each line displayed unique combinations of site-specific markers, including AJAP1, ALDH1A2, MPS, BARX1, HAND2, HOXB2, LHX1, LHX8, PITX1, TBX15 and ZIC2, but none of the lines expressed the MSC marker CD74. The lines showed diverse responses when differentiated in the presence of combinations of TGF-beta 3, BMP2, 4, 6 and 7 and GDF5, with the lines 4D20.8, SK11, SM30 and MEL2 showing osteogenic markers in some differentiation conditions. The line 7PEND24 showed evidence of regenerating articular cartilage and, in some conditions, markers of tendon differentiation. Conclusion: The scalability of site-specific clonal human embryonic stem cell-derived embryonic progenitor cell lines may provide novel models for the study of differentiation and methods for preparing purified and identified cells types for use in therapy.

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