miRNA profiling of NurOwn®: mesenchymal stem cells secreting neurotrophic factors

Stem Cell Res Ther. 2017 Nov 7;8(1):249. doi: 10.1186/s13287-017-0692-1.


Background: MSC-NTF cells are Mesenchymal Stromal Cells (MSC) induced to express high levels of neurotrophic factors (NTFs) using a culture-medium based approach. MSC-NTF cells have been successfully studied in clinical trials for Amyotrophic Lateral Sclerosis (ALS) patients. MicroRNAs (miRNA) are short non-coding RNA molecules that coordinate post-transcriptional regulation of multiple gene targets. The purpose of this study was to determine whether the miRNA profile could provide a tool for MSC-NTF cell characterization and to distinguish them from the matched MSC from which they are derived.

Methods: NTF secretion in the culture supernatant of MSC-NTF cells was evaluated by ELISA assays. The Agilent microarray miRNA platform was used for pairwise comparisons of MSC-NTF cells to MSC. The differentially expressed miRNAs and putative mRNA targets were validated using qPCR analyses.

Results: Principal component analysis revealed two distinct clusters based on cell type (MSC and MSC-NTFs). Nineteen miRNAs were found to be upregulated and 22 miRNAs were downregulated in MSC-NTF cells relative to the MSC cells of origin. Further validation of differentially expressed miRNAs confirmed that miR-3663 and miR-132 were increased 18.5- and 4.06-fold, respectively while hsa-miR-503 was reduced more than 15-fold, suggesting that miRNAs could form the basis of an MSC-NTF cell characterization assay. In an analysis of the miRNA mRNA targets, three mRNA targets of hsa-miR-132-3p (HN-1, RASA1 and KLH-L11) were found to be significantly downregulated.

Conclusions: We have demonstrated that MSC-NTF cells can be distinguished from their MSCs of origin by a unique miRNA expression profile.

Trial registration: Clinicaltrial.gov identifier NCT01777646 . Registered 12 December 2012.

Keywords: Amyotrophic Lateral Sclerosis; Mesenchymal Stromal Cells; MicroRNAs; Neurotrophic Factors.

MeSH terms

  • Cell Differentiation
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism*
  • Nerve Growth Factors / metabolism*


  • MicroRNAs
  • Nerve Growth Factors

Associated data

  • ClinicalTrials.gov/NCT01777646