Bone marrow mononuclear cells, an important player in peripheral nerve regeneration

PAULA A. SOTO; MARCELA B. FERNÁNDEZ VAN RAAP; VANINA USACH; GONZALO PIÑERO; PABLO BRUMOVSKY; MAILIN CASADEI; MARIANELA VENCE; PATRICIA SETTON-AVRUJ

Evento virtual

Ronda de negocios; International Congress of Translational Medicine; 2021

SAN

Peripheral neuropathies have high incidence worldwide and are typically associated with degeneration of myelin and axons plus immune cell infiltration. The clinical presentation of peripheral neuropathies includes partial or total functional loss of the affected limb and neuropathic pain. The use of stem cells for the regeneration of damaged peripheral nerves represents a promising therapeutic approach and a field of intensive study. In particular, bone marrow mononuclear cells (BMMC) are emerging as an interesting option in regenerative medicine. BMMC are a heterogeneous fraction containing a small population of multipotent cells and are good candidates for cell therapy because of their convenient isolation protocol, high yield and survival rate after transplantation and low immunogenicity. We have previously demonstrated the spontaneous migration of endogenous CD34+ multipotent cells both in a reversible (8 sec crush) and irreversible (ligation) model of Wallerian Degeneration. The aim of the present work is to evaluate if the systemic transplantation or endogenous mobilization of BMMC could represents a potential therapeutic approach for the control of the clinical presentation of various type of sciatic nerve injury. For this, adult rats were subjected to different experimental models of sciatic nerve damage and morphological, functional and pain behavior parameters analysis. The models evaluated were: 8 or 30 sec crush and the spared nerve injuri (SNI) models, followed by immediate or delayed BMMC transplant. In addition, selective targeting of BMMC into injured nerves also tested by use of magnetic nanoparticles-loaded BMMC. Independetly of the model, BMMC migrated exclusively to the injured nerve and were able to prevent or revert the neuropathic pain associated to the injury. BMMC also demonstrated beneficial effects in terms of morphology, compound muscle action potential and sciatic functional index. These effects were particularly potentiated upon use of magnetic nanoparticles-loaded BMMC and magnetic stimulation. Pharmacological stimulation of endogenous CD34+ cell migration through AMD3100 also demonstrated a recovery in myelin protein organization in terms of MBP and PMP22, 7 days post injury. These results support that the systemic transplant or the pharmacological mobilization of BMMC may be a promising strategy for the treatment of acquired peripheral neuropathies.