Influence of Delivery Method on Neuroprotection by Bone Marrow Mononuclear Cell Therapy following Ventral Root Reimplantation with Fibrin Sealant

Abstract

The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results.

Long-Term Spinal Ventral Root Reimplantation, but not Bone Marrow Mononuclear Cell Treatment, Positively Influences Ultrastructural Synapse Recovery and Motor Axonal Regrowth

“…This indicates that the fibrin sealant implant provided conditions for regeneration of nerve fibers, resulting in a close to normal “g” ratio distribution. These results are in accordance with already published data by our group, where improvement in motor function was observed at 12 weeks after reimplantation of avulsioned roots [ 18 , 27 ]. MC treatment, however, resulted in decreased RZG, which will be addressed in future short-term analysis.…”

“…The results were observed by immunohistochemistry, in a semiquantitative fashion, indicating a significant enhancement of root axonal regrowth, two weeks after surgery. Such results are in line with a recent work from our lab, using mononuclear cells from the bone marrow [ 18 ]. Nevertheless, we have shown that the acute positive results of cell therapy do not last for more than four weeks, indicating that additional cell administration may be necessary to sustain the protective results.…”

Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

“…This may be achieved by stem cell therapy that has shown particularly important positive effects following nervous system injury [ 28 – 37 ]. In this regard, we have already shown evidence that mononuclear cell therapy produced neuroprotection, preservation of synapses in the spinal cord, and reduction of glial reaction following dorsal and ventral horn adult lesion [ 38 , 39 ].…”

Translational Medicine in Tissue Regeneration

“…In addition, translational research generates an increase in the capacity for health research with an interdisciplinary and multidisciplinary approach, forming, training and integrating a new generation of researchers [4]. This new biopharmaceutical has enormous potential application in Medicine and Dentistry [10], which presents greater purity, lesser toxicity and greater adhesiveness [11][12][13][14][15].…”