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.
Highlights
In order to enhance the success of adult stem cell (SC) translational medicine efforts, the source as well as the most effective delivery method has to be considered
The peripheral nerve regeneration after mononuclear cells (MC) has been connected to the local production of neurotrophic factors [1,3,4]
2.5- Mononuclear cells transplantation In group 3 (AV+S+HC), 36105 MCs were added to the fibrin sealant in avulsed roots reimplantation at the moment of implantation
Summary
In order to enhance the success of adult stem cell (SC) translational medicine efforts, the source as well as the most effective delivery method has to be considered. In order to improve the outcome following VRA, regarding neuronal survival, several attempts have been made to provide neurotrophic molecules at the site of injury. In this regard, the association of the root reimplantation with BDNF and CNTF resulted in rescue of injured motoneurons after avulsion in rabbits [17]. It is improbable that a single neurothrophic molecule will be sufficient to provide the necessary conditions for optimal regeneration Based on such facts, the advent of stem cell technology brought new insights on cell therapy and local delivery of trophic substances. The administration method significantly influenced treatment outcome, so that the use of fibrin sealant MC delivery approach gave the best and more long lasting results
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