"INTRODUCTION: Iron oxide based magnetic nanomaterial, magnetic nanoparticles (MNPs) and magnetic nanowires (NW) are versatile tools in biology and medicine. MNPs-mediated drug delivery is tested for regenerative medicine (RM) purposes as well as for tumour treatment and diagnostics. Stem cell mediated delivery represents a modality to target remote, metastatic tumors or regenerative sites for controlled drug delivery. We recently reported that emote controlled actuation of MNPs-loaded cells can deliver micro-mechanical stimulation for modulating mesenchymal stem cell differentiation potential. NW platforms can be used to deliver topographical cues as well as magnetomechanical stimulation to differentiating MSCs.
METHODS: Human adipose derived stem cells (ADSCs) and Wharton jelly derived MSCs (WJMSC) loaded with proprietary were tested for viability, proliferative capabilities, culture induced senescence (beta galactosidase assay) and magnetic properties. In vitro osteogenic adipogenic potential of ADSCs-MNP as well as chondrogenic potential of ADSC and WJMSC –MNP exposed to magnetic field (MF) was tested. ADSC cultured on NW substrates with or without MF exposure were tested for viability and differentiation potential to mesenchymal lineages.
RESULTS: ADSCs-MNP and WJMSC-MNP complexes retain cell viability and proliferative capabilities compared to non-loaded and become controllable within MF due to high iron content. MNP presence decrease stem cells culture induced senescence. ADSCs–MNP display increased osteogenic and decreased adipogenesis when exposed to alternating magnetic field in a time, modality of exposure and MF intensity manner. ADSC-MNP displayed increased chondrogenesis compared to WJMSCs further increased by MF exposure. NW substrate supports attachment and viability of ADSC. Osteogenic conversion of ADSC cultured on NW substrates was found to be increased compared to plastic culture dish.
DISCUSSION & CONCLUSIONS: ADSCs-MNP display increased osteogenic and decreased adipogenic potential under alternating MF dependently on exposure protocol. ADSC-MNP but not WJMSC display increased chondrogenesis in vitro, further increased by MF exposure. NW substrate can be used to enhance osteogenic potential of ADSC in vitro. While this findings need to be confirmed in vivo experiments, MNP loading and NW substrated can be used to design innovative modalities for engineering of implantable bone and cartilage.
This work was supported by a grant of the Ministry of Research, Innovation and Digitization, CNCS/CCCDI - UEFISCDI, project number ERANET-EURONANOMED-3-OASIs, within PNCDI III"" and:"" NUCLEU Program (PN 19 28 01 01)"".