title: Enhancement of median nerve regeneration by mesenchymal stem cells engraftment in an absorbable conduit: improvement of peripheral nerve morphology with enlargement of somatosensory cortical representation.
abstract: We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm(2), respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm(2)). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil.
authors.forename: Julia T
authors.initials: JT
authors.lastname: Oliveira
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora Juiz de Fora, Brazil.
authors.forename: Ruben Ernesto
authors.initials: RE
authors.lastname: Bittencourt-Navarrete
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil ; Universidade Federal do Rio de Janeiro Macaé, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: de Almeida
authors.affiliation: Department of Mechanical and Aerospace Engineering, Politecnico di Torino Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tonda-Turo
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil ; Departamento de Anatomia Patológica, Faculdade de Medicina, e Pós Graduação em Anatomia Patológica, Centro de Ciências da Saúde, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil.
authors.forename: Ana Maria B
authors.initials: AM
authors.lastname: Martinez
authors.affiliation: Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil.
authors.forename: João G
authors.initials: JG
authors.lastname: Franca
keywords: cortical plasticity; median nerve lesion; nerve regeneration; polycaprolactone conduits; rat; stem-cell therapy