Abstract Details

Title Molecular Characterization of VEGF Secretion by MSC-NTF Cells (NurOwn®): Therapeutic Implications in ALS

Topic Autoimmune Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-081

Objective

To evaluate the molecular characterization of VEGF secretion by MSC-NTF cells (NurOwn^®) and report on the potential therapeutic implications in ALS.

Background MSC-NTF cells (NurOwn^®) are autologous bone marrow derived mesenchymal stem cells (MSCs) induced in culture to secrete high levels of neurotrophic factors (NTFs) that support neuronal growth and survival. Thus, MSC-NTF cells combine MSC's immunomodulatory therapeutic benefits with enhanced neurotrophic factor secretion. A phase 3 randomized clinical trial is in progress at 6 sites in the U.S. to evaluate the efficacy and safety of repeated intrathecal (IT) administration of MSC-NTF cells in ALS patients (NCT03280056). As previously reported, VEGF has an important immunomodulatory and neuroprotective role in ALS through biological effects on microglia and glutamatergic disease mechanisms.

Design/Methods To explore the molecular differences between naïve MSC and MSC-NTF cells, we performed mass-spectrometry proteomics, Affymetrix gene arrays and microRNA arrays. To map changes in protein secretion, ELISA assays were employed. Subsequently, several bioinformatic tools were applied to investigate the interactions between protein secretion, protein/gene expression and microRNAs.

Results Differentiation of MSCs into MSC-NTF cells resulted in >6-fold increase in VEGF, HGF and GDNF secretion. microRNA (miRNA) array data revealed that out of 21 downregulated MSC-NTF cell microRNAs, 7 are predicted to target VEGF. These include miR-320a and 424-5p which were previously reported to target VEGF. In addition, analysis of proteomics data revealed the central role of VEGF in the network of proteins which are upregulated in MSC-NTF cells.

Conclusions There are significant differences in protein and microRNA expression levels between MSCs and MSC-NTF cells that may contribute to NurOwn^®’s mechanism of action. Changes in microRNA expression are likely to contribute to increased VEGF secretion in MSC-NTF cells. The significantly increased secretion of VEGF and other NTFs by MSC-NTF cells may contribute to key ALS neuroprotective and immunomodulatory therapeutic mechanisms.

Authors/Disclosures
PRESENTER	No disclosure on file
Revital Aricha	Revital Aricha has nothing to disclose.
	No disclosure on file
Yael Gothelf	Yael Gothelf, 18041 has received personal compensation for serving as an employee of Brainstorm Cell Therapeutics.
Chaim Lebovits (BrainStorm Cell Therapeutics)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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