Comparison of human olfactory and skeletal MSCs using osteogenic nanotopography to demonstrate bone-specific bioactivity of the surfaces.

Recently we identified a novel population of mesenchymal stem cells (MSCs) from human olfactory mucosa (OM-MSCs), a tissue which promotes neurogenesis throughout life, and demonstrated that they promoted CNS myelination to a greater extent than bone marrow-derived (BM)-MSCs. Previous data demonstrated that nanotopographies with a degree of disorder induce BM-MSC osteogenic differentiation. Thus, using biomaterials as non-chemical tools, we investigated if MSCs from a completely different cellular niche could be induced to differentiate similarly to nanoscale cues alone. Both MSCs differentiated into bone when cultured on nanotopographically embossed polycaprolactone (PCL) with a disordered pattern and heights but not on a "smooth" non-embossed PCL control substrate, but OM-MSC changes were at lower expression levels. Both MSCs showed similar increases in differentiation markers at the protein and mRNA level when plated on the two patterned surfaces. Thus, topographical cues from substrates with disordered patterns can up-regulate several MSC resident genes in both BM-MSCs and OM-MSCs. Moreover, antibody purified BM-MSCs had similar properties to non-purified BM-MSCs. These data suggest that MSCs from a neural cellular niche express similar bone-induced cues to BM-MSCs, suggesting that MSCs that inherently support nervous tissue can differentiate along the bone lineage in a similar manner to MSCs from a skeletal environment.

Human mesenchymal stem cells isolated from olfactory biopsies but not bone enhance CNS myelination in vitro.

Spinal cord injury (SCI) is a devastating condition with limited capacity for repair. Cell transplantation is a potential strategy to promote SCI repair with cells from the olfactory system being promising candidates. Although transplants of human olfactory mucosa (OM) are already ongoing in clinical trials, the repair potential of this tissue remains unclear. Previously, we identified mesenchymal-like stem cells that reside in the lamina propria (LP-MSCs) of rat and human OM. Little is known about these cells or their interactions with glia such as olfactory ensheathing cells (OECs), which would be co-transplanted with MSCs from the OM, or endogenous CNS glia such as oligodendrocytes. We have characterized, purified, and assessed the repair potential of human LP-MSCs by investigating their effect on glial cell biology with specific emphasis on CNS myelination in vitro. Purified LP-MSCs expressed typical bone marrow MSC (BM-MSC) markers, formed spheres, were clonogenic and differentiated into bone and fat. LP-MSC conditioned medium (CM) promoted oligodendrocyte precursor cell (OPC) and OEC proliferation and induced a highly branched morphology. LP-MSC-CM treatment caused OEC process extension. Both LP and BM-MSCs promoted OPC proliferation and differentiation, but only myelinating cultures treated with CM from LP and not BM-MSCs had a significant increase in myelination. Comparison with fibroblasts and contaminating OM fibroblast like-cells showed the promyelination effect was LP-MSC specific. Thus LP-MSCs harvested from human OM biopsies may be an important candidate for cell transplantation by contributing to the repair of SCI.