Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials

Abstract

Purpose Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation. Methods Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system. Results We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system. Conclusion Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.

Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells

“…Some studies report BDNF to support motor and sensory neuron survival (neuroprotective effects) besides promoting the regeneration of axons in sensory and motor neurons [ 23 ]. On the other hand, it is known that GDNF enhances the survival and outgrowth of both motor and sensory neurons [ 6 ] as well as stimulates axon sparing and regeneration [ 24 ]. NGF is neuroprotective and promotes neurite outgrowth of sensory and sympathetic neurons in vitro and in vivo [ 25 ].…”

Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment

“…Immortalized neuronal cell lines such as PC12, a neural cell line derived from pheochromocytoma of rat adrenal medullary, have been used for this purpose. This cell line shows a pro-regenerative potential when several compounds are tested in neurite outgrowth assays ( Greene and Tischler, 1976 ; Haastert-Talini et al, 2014 ). 50B11 is a sensory neuron cell line isolated from rat embryonic DRG ( Chen et al, 2007 ).…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…Hence, IONP-labelling of stem cells or other cells, such as astrocytes and microglia can be used to track and monitor transplanted cells after implantation, e.g., by a noninvasive imaging modality such as MRI, magnetic particle imaging, positron emission tomography, and multiple photon microscopy [391][392][393][394][395][396][397][398][399][400][401][402]. Moreover, IONPs and IONP-loaded cells allow the delivery of therapeutic biomolecules, such as neurotrophic factors, drugs, proteins, DNA and siRNA by specific NP functionalization [403][404][405][406][407]. Functionalized IONPs and IONP-loaded cells can be effectively enriched at the injury site by external magnet fields to efficiently promote neuronal repair or guide axonal growth [408][409][410][411][412][413][414][415].…”