Adipose-derived mesenchymal stem cells magnetic targeting to promote sciatic nerve regeneration after traumatic injury

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

CABA

Congreso; First Meeting Glia Club Southern Cone: The good, the bad, the nice and the ugly of glial cells.; 2022

Club de la Glia

Traumatic peripheral nerve lesions constitute a major concern in public health with high prevalence worldwide. Despite the regenerative capability of the peripheral nervous system, sometimes poor clinical evolution turns these affections into a disabling disease, which is why the development of new regenerative therapies is of great importance. Wallerian degeneration (WD) is an efficient experimental model which mimics the impact of peripheral nerve lesion, usually used to shed light on possible regeneration strategies.Adipose-derived mesenchymal stem cells (AdMSC) are multipotent adult stem cells which are being fully investigated for regenerative therapies and appear as a promising tool due to their multiple advantages as multipotentiality, low immunogenicity and low invasive isolation. On the other hand, magnetic targeting (MT) is a nanotechnological strategy to mobilize magnetic nanoparticles (MNP), or ?magnetized? cells - cells loaded with MNP - using static magnetic fields. In this context, the aim of the present work was to test in an in vivo WD model whether magnetic targeting can optimize cell recruitment of systemically transplanted AdMSC loaded with MNP (AdMSC-MNP) in the lesion area through an external magnetic field, and thus improve the regenerative ability of AdMSC upon sciatic nerve lesion.The WD model was promoted by the compression of the sciatic nerve. AdMSC and AdMSC-MNP arrival at the injured nerve were evaluated through microscopy and magnetometry. Also, cell transplantation effects on regeneration were evaluated both in terms of nerve morphology and function by the measurement of the distal latency and amplitude of the compound muscle action potential (CMAP).Our results show that AdMSC can internalize 2-4 pg MNP/cell and that AdMSC-MNP are magnetically attracted and retained exclusively at the injured nerve, enhancing cell arrival and their beneficial effects. Animals treated with AdMSC-MNP and MT showed a partially conserved nerve structure with many intact myelinated axons. Also, a remarkable restoration in myelin basic protein organization, indicative of remyelination, was observed. This resulted in an improvement in nerve conduction, demonstrating functional recovery.In short, our results prove that magnetic targeting of AdMSC-MNP constitutes a novel and valuable tool to promote nerve regeneration by enhancing AdMSC arrival at the lesion site