Effects of late bone marrow mononuclear cell transplantation in rats with sciatic nerve crush.Analysis of a potential therapeutic time window.

VANINA USACH; MAILIN CASADEI; GONZALO PIÑERO; MARIANELA VENCE; PABLO R. BRUMOVSKY; CLARA P. SETTON

Virtual

Congreso; XXXV Congreso Anual Sociedad Argentina de Neurociencias (SAN), virtual; 2020

Sociedad Argentina de Investigación en Neurociencias

When systemically transplanted after lesion, multipotent bone marrow cells (BMMC) migrate spontaneously to the injured sciatic nerve, as observed in a model of reversible sciatic nerve crush. Once at the Ipsilateral nerve, BMMC promote regeneration in terms of morphology, slightly improve the amplitude of compound muscle action potential and fully prevent injury-associated neuropathic pain. So as to propose systemic BMMC transplant as a potential therapeutic strategy, the aim of the present work is to determine the most adequate moment for BMMC transplant after injury to optimize their effects on nerve regeneration. Adult Wistar rats submitted to 8-second sciatic nerve crush were systemically transplanted with BMMC at different survival times post lesion and sacrificed 7 days after transplant. Cell recruitment was confirmed by confocal microscopy and transplant effects were evaluated only in animals transplanted 7 days post injury. Results show the highest number of BMMC recruited into the ipsilateral nerve when transplanted at the peak of demyelination, 7 days post injury. Partial recovery was observed in terms of myelin and axonal protein organization and levels; with no effects on sciatic functional index detected. However, a remarkable and sustained reduction in mechanical and cold allodynia was promoted by late BMMC transplant. Further experiments are guaranteed to establish the best timing for late BMMC transplant towards treatment of peripheral demyelination processes.