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

Regen Med. 2013 Mar;8(2):125-44. doi: 10.2217/rme.12.117. Epub 2012 Dec 18.

Abstract

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, BMP5, 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-β3, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Lineage* / drug effects
  • Cell Lineage* / genetics
  • Chondrocytes / metabolism
  • Chondrogenesis* / drug effects
  • Chondrogenesis* / genetics
  • Clone Cells
  • Collagen Type II / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Proteoglycans / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Staining and Labeling
  • Stem Cell Transplantation
  • Tissue Engineering
  • Transforming Growth Factor beta / pharmacology

Substances

  • Antigens, CD
  • Biomarkers
  • Collagen Type II
  • Proteoglycans
  • RNA, Messenger
  • Transforming Growth Factor beta