MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors

Nicole Georgi, H. Taipaleenmaeki, C.C. Raiss, N. Groen, K.K. Portalska, Clemens van Blitterswijk, Jan de Boer, Janine Nicole Post, A. van Wijnen, Hermanus Bernardus Johannes Karperien

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Abstract

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. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. Here, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty human MSC donors were initially tested for marker expression and differentiation potential. In particular, 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 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 seven-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 prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.
Original languageEnglish
Pages (from-to)1946-1955
Number of pages47
JournalStem cells and development
Volume24
Issue number16
DOIs
Publication statusPublished - 27 Apr 2015

Fingerprint

Differentiation Antigens
MicroRNAs
Mesenchymal Stromal Cells
Chondrogenesis
Messenger RNA
Cell Lineage
Glycosaminoglycans
Cartilage
Regeneration
Homeostasis
Biomarkers

Keywords

  • METIS-310545
  • IR-95940

Cite this

Georgi, Nicole ; Taipaleenmaeki, H. ; Raiss, C.C. ; Groen, N. ; Portalska, K.K. ; van Blitterswijk, Clemens ; de Boer, Jan ; Post, Janine Nicole ; van Wijnen, A. ; Karperien, Hermanus Bernardus Johannes. / MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors. In: Stem cells and development. 2015 ; Vol. 24, No. 16. pp. 1946-1955.
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abstract = "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. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. Here, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty human MSC donors were initially tested for marker expression and differentiation potential. In particular, 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 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 seven-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 prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.",
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Georgi, N, Taipaleenmaeki, H, Raiss, CC, Groen, N, Portalska, KK, van Blitterswijk, C, de Boer, J, Post, JN, van Wijnen, A & Karperien, HBJ 2015, 'MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors', Stem cells and development, vol. 24, no. 16, pp. 1946-1955. https://doi.org/10.1089/scd.2014.0534

MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors. / Georgi, Nicole; Taipaleenmaeki, H.; Raiss, C.C.; Groen, N.; Portalska, K.K.; van Blitterswijk, Clemens; de Boer, Jan; Post, Janine Nicole; van Wijnen, A.; Karperien, Hermanus Bernardus Johannes.

In: Stem cells and development, Vol. 24, No. 16, 27.04.2015, p. 1946-1955.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Georgi, Nicole

AU - Taipaleenmaeki, H.

AU - Raiss, C.C.

AU - Groen, N.

AU - Portalska, K.K.

AU - van Blitterswijk, Clemens

AU - de Boer, Jan

AU - Post, Janine Nicole

AU - van Wijnen, A.

AU - Karperien, Hermanus Bernardus Johannes

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N2 - 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. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. Here, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty human MSC donors were initially tested for marker expression and differentiation potential. In particular, 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 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 seven-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 prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.

AB - 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. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. Here, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty human MSC donors were initially tested for marker expression and differentiation potential. In particular, 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 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 seven-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 prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.

KW - METIS-310545

KW - IR-95940

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DO - 10.1089/scd.2014.0534

M3 - Article

VL - 24

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EP - 1955

JO - Stem cells and development

JF - Stem cells and development

SN - 1547-3287

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Georgi N, Taipaleenmaeki H, Raiss CC, Groen N, Portalska KK, van Blitterswijk C et al. MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors. Stem cells and development. 2015 Apr 27;24(16):1946-1955. https://doi.org/10.1089/scd.2014.0534