Using magnetically targeted Adipose-derived Mesenchymal Stem Cells to promote sciatic nerve regeneration

PAULA A, SOTO; MARCELA FERNANDEZ VAN RAAP; CLARA P. SETTON

Virtual

Conferencia; Spanish Conference on Biomedical Applications of Nanomaterials; 2021

Traumatic peripheral nerve injuries constitute a huge concern to public health. Nerve damage leads to a decrease or even loss of mobility of the innervated area. Due to their complex pathophysiology, current pharmacological and surgical approaches are only partially effective. Cell-based therapies emerged as a useful tool to reach full tissue regeneration. In this context, adult stem cell therapies have provided some encouraging outcomes and are identified as promising agents to treat nerve injuries, promoting nerve regeneration. However, a major bottleneck of that approach is to secure a sufficient number of cells at the injured site to warrant measurable therapeutic effects. The present work tackles this issue combining biological (adipose derived mesenchymal stem cells, AdMSC) and nanotechnological strategies (magnetic targeting) to demonstrate whether a higher number of recruited multipotent cells promotes nerve regeneration in an in vivo model of Wallerian degeneration.To this end, AdMSC were loaded with citric acid coated superparamagnetic iron oxide nanoparticles (SPIONs), systemically transplanted and magnetically recruited to the injured sciatic nerve (Figure 1). AdMSC arrival and retention to the injured nerve was significantly stimulated by magnetic targeting and their beneficial effects surpass the regenerative properties of the stand-alone cell therapy. AdMSC-SPIONs group shows a partially conserved nerve structure with many intact myelinated axons. From a molecular point of view, a remarkable restoration in myelin basic protein organization, indicative of remyelination, was observed which brought about a clear increase in the distal latency of the compound muscle action potential, as a sign of functional recovery. In summary, our results demonstrate that magnetically assisted delivery of AdMSC, using a non-invasive and non-traumatic method, is a highly promising strategy to promote cell recruitment and sciatic nerve regeneration after traumatic injury