AUTHOR=Okolicsanyi Rachel K. , Oikari Lotta E. , Yu Chieh , Griffiths Lyn R. , Haupt Larisa M. 

TITLE=Heparan Sulfate Proteoglycans as Drivers of Neural Progenitors Derived From Human Mesenchymal Stem Cells

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=11

YEAR=2018

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2018.00134

DOI=10.3389/fnmol.2018.00134

ISSN=1662-5099

ABSTRACT=<p><bold>Background:</bold> Due to their relative ease of isolation and their high <italic>ex vivo</italic> and <italic>in vitro</italic> expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation.</p><p><bold>Methods:</bold> Following the determination that hMSCs maintain neural potential throughout extended <italic>in vitro</italic> expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs. hMSCs cultured in basal conditions (undifferentiated monolayer cultures) were found to co-express neural markers and HSPGs throughout expansion with modulation of the <italic>in vitro</italic> niche through the addition of exogenous HS influencing cellular HSPG and neural marker expression.</p><p><bold>Results:</bold> Conversion of hMSCs into hMSC Induced Neurospheres (hMSC IN) identified distinctly localized HSPG staining within the spheres along with altered gene expression of HSPG core protein and biosynthetic enzymes when compared to undifferentiated hMSCs.</p><p><bold>Conclusion:</bold> Comparison of markers of pluripotency, neural self-renewal and neural lineage specification between hMSC IN, hMSC and human neural stem cell (hNSC H9) cultures suggest that <italic>in vitro</italic> generated hMSC IN may represent an intermediary neurogenic cell type, similar to a common neural progenitor cell. In addition, this data demonstrates HSPGs and their biosynthesis machinery, are associated with hMSC IN formation. The identification of specific HSPGs driving hMSC lineage-specification will likely provide new markers to allow better use of hMSCs in therapeutic applications and improve our understanding of human neurogenesis.</p>