Bone marrow mononuclear cells transplantation: a useful tool to promote regeneration and remyelination in the peripheral nervous system.

PIÑERO, GONZALO; MONJE, PAULA; USACH, VANINA; SETTON-AVRUJ, CLARA P.; SOTO, PAULA

Conferencia; The role of glial cells in health and disease of the Nervous System: Clinical and Basic Science walking together; 2017

Lithium salts have been the conventional pharmacological treatment for bipolar disorder for over six decades. Additional benefits include neuroprotective, anti-inflammatory, and anti-apoptotic effects, which have been exploited to treat central nervous system trauma and chronic neurodegenerative diseases. In the peripheral nervous system, lithium administration has been shown to foster functional recovery and remyelination after injury. Our group has studied the bioactivity, specificity, and reversibility of lithium?s action on cultured Schwann cell (SC) growth, survival, proliferation and differentiation, in addition to basal lamina and myelin formation in SC-neuron cultures. On the other hand, our group has demonstrated in a model of sciatic nerve crush that systemically transplanted bone marrow mononuclear cells (BMMC) spontaneously migrate to and remain in the injured nerve for as long as 60 days post injury (dpi). Once in the ipsilateral nerve, some of the cells colocalized with SC markers. BMMC were also shown to exert a beneficial effect on axon regeneration and remyelination and prevent hyperalgesia. In the present work, we combined these two potential treatments. After nerve compression, animals received intravenous transplantation of BMMC and orally administered LiCl. Axonal regeneration, remyelination and functional recovery were analyzed 14 dpi. While combined therapy did not exhibit differences regarding BMMC treatment in terms of myelin recovery, analyzed through immunohistochemistry or western blot; preliminary electron microscopy studies showed smaller but more highly myelinated axons in the combined therapy group. Further assays currently under way will corroborate the advantages of combined therapy over single treatment.