MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors.
The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Since the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. In this study, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty hMSC donors were initially tested for marker expression and differentiation potential. In particular, the chondrogenic differentiation potential was evaluated on the basis of histological matrix formation, mRNA expression levels of chondrogenic marker genes, and quantitative glycosaminoglycan deposition. Three donors out of twenty were identified as donors with high chondrogenic potential, whereas nine showed moderate and eight showed low chondrogenic potential. Expression profiles of miRNAs involved in chondrogenesis and cartilage homeostasis were used for the distinction between high-performance hMSCs and low-performance hMSCs. Global mRNA expression profiles of the donors before the onset of chondrogenic differentiation revealed minor differences in gene expression between low and high chondrogenic performers. However, analysis of miRNA expression during a 7-day differentiation period identified miR-210 and miR-630 as positive regulators of chondrogenesis. In contrast, miR-181 and miR-34a, which are negative regulators of chondrogenesis, were upregulated during differentiation in low-performing donors. In conclusion, profiling of hMSC donors for a specific panel of miRNAs may have a prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.
1 Department of Developmental BioEngineering, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Nicole
N
Georgi
2 Heisenberg-Group for Molecular Skeletal Biology, Department of Trauma-, Hand- and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
Hanna
H
Taipaleenmaki
3 Nanobiophysics Group, Faculty of Science and Technology, MESA+Institute for Nanotechnology, University of Twente , Enschede, the Netherlands .
Christian C
CC
Raiss
4 Department of Tissue Regeneration, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Nathalie
N
Groen
4 Department of Tissue Regeneration, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Karolina Janaeczek
KJ
Portalska
4 Department of Tissue Regeneration, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Clemens
C
van Blitterswijk
4 Department of Tissue Regeneration, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Jan
J
de Boer
1 Department of Developmental BioEngineering, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Janine N
JN
Post
5 Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic , Rochester, Minnesota.
Andre J
AJ
van Wijnen
1 Department of Developmental BioEngineering, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Marcel
M
Karperien
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D014019:Tissue Donors; D059467:Transcriptome
D015415:Biomarkers; D035683:MicroRNAs