title: Superior osteogenic capacity of human embryonic stem cells adapted to matrix-free growth compared to human mesenchymal stem cells.
abstract: Human mesenchymal stem cells (hMSCs) represent a promising source of cells for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. An alternative is the use of human embryonic stem cells (hESCs), but labor-intensive expansion with the need for coating support limits their clinical use. We have previously derived a cell line from hESCs denoted matrix-free growth (MFG)-hESC that are independent of coating support for expansion, and we here compare its osteogenic capacity to that of hMSCs. Microarray analysis of hMSCs and MFG-hESCs revealed differential expression of genes involved in ossification. MFG-hESCs have significantly higher expression of secreted phosphoprotein 1 (SPP1) during osteogenic differentiation, whereas the opposite was true for alkaline phosphatase (ALPL), transforming growth factor, beta 1 (TGFB2), runt-related transcription factor 2 (RUNX2), and forkhead box C1 (FOXC1), as well as the activity of the ALPL enzyme, demonstrating that these two cell types differentiate into the osteogenic lineage using different signaling pathways. von Kossa staining, time-of-flight secondary ion mass spectrometry, and measurement of calcium and phosphate in the extracellular matrix demonstrated a superior ability of the MFG-hESCs to produce a mineralized matrix compared to hMSCs. The superior ability of the MFG-hESCs to form mineralized matrix compared to hMSCs demonstrates that MFG-hESCs are a promising alternative to the use of adult stem cells in future bone regenerative applications.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden. narmin.bigdeli@gu.se
authors.forename: Narmin
authors.initials: N
authors.lastname: Bigdeli
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: de Peppo
authors.forename: Maria
authors.initials: M
authors.lastname: Lennerås
authors.forename: Peter
authors.initials: P
authors.lastname: Sjövall
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.forename: Johan
authors.initials: J
authors.lastname: Hyllner
authors.forename: Camilla
authors.initials: C
authors.lastname: Karlsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018629:Spectrometry, Mass, Secondary Ion
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase