Influence of delivery method on neuroprotection by bone marrow mononuclear cell therapy following ventral root reimplantation with fibrin sealant

PLoS One. 2014 Aug 26;9(8):e105712. doi: 10.1371/journal.pone.0105712. eCollection 2014.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cranial Nerve Injuries
  • Female
  • Fibrin Tissue Adhesive / therapeutic use*
  • Gene Expression
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Leukocytes, Mononuclear / transplantation*
  • Microglia / physiology
  • Nerve Tissue / transplantation
  • Rats, Inbred Lew
  • Recovery of Function
  • Spinal Nerve Roots / pathology

Substances

  • Brain-Derived Neurotrophic Factor
  • Fibrin Tissue Adhesive
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Fibrillary Acidic Protein

Grants and funding

The present work was supported by a grant from Fundação de Amparo a Pesquisa do Estado de São Paulo – FAPESP, Brazil (2010/0986-5). Barbizan R. was supported by Fundação de Amparo a Pesquisa do Estado de Sao Paulo – FAPESP (process number: 2010/00729-2). This work was funded by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.