A safe and low-invasive method for sciatic nerve remyelination: magnetic targeting of adult mesenchymal stem cells

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

Virtual

Congreso; V International Congress in Translational Medicine, IMBS; 2021

IMBS

Sciatic nerve traumatic injuries constitute a common problem of public health with high prevalenceworldwide. Current therapeutic approaches fail to restore the normal nerve functions, that is why the development of new therapies is of great importance.Although adult stem cell therapies have provided encouraging results in nerve regeneration, the major obstacle of getting enough cells to the injured site to guarantee therapeutic effects remains to be overcome.Here, we proposed an interdisciplinary strategy combining adipose derived mesenchymal stem cells(AdMSC) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to enhance theirmobility towards the injured sciatic nerve by external manipulation with the application of a magnetic field gradient (magnetic targeting, MT).The aim of the present work was to test whether magnetic targeting can help SPIONs internalized by AdMSC (AdMSC-SPIONs) reach specific tissue and thus improve the regenerative ability of AdMSC upon sciatic nerve lesion.To this end, AdMSC, SPIONs, and AdMSC-SPIONs were extensively characterized. AdMSCSPIONs arrival and retention at the injured sciatic nerve were evaluated through dc-magnetometry,confocal and transmission electron microscopy (TEM). Finally, cell transplantation effects onregeneration were assessed both in terms of nerve morphology using immunofluorescence andwestern blot and nerve impulse conduction.We observed a significant increase in AdMSC arrival to the injured nerve using MT, and inconsequence their beneficial effects surpassed the regenerative properties of the stand-alone celltherapy. TEM images of AdMSC-SPIONs group show many intact myelinated axons. Also, a veryremarkable restoration in myelin basic protein organization, indicative of remyelination and animprovement in nerve conduction values compared to the non-treated group, were observed.In short, our results prove that magnetic targeting of AdMSC-SPIONS constitutes a novel and lowinvasive method to promote sciatic nerve regeneration by enhancing AdMSC arrival at the lesion site, in the peripheral nervous system.