Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis

In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), different...

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Main Authors: T. Pereira, A. Gärtner, I. Amorim, A. Almeida, A. R. Caseiro, Paulo A. S. Armada-da-Silva, Sandra Amado, Federica Fregnan, A. S. P. Varejão, J. D. Santos, P. J. Bartolo, S. Geuna, A. L. Luís, A. C. Mauricio
Format: Article
Language:English
Published: Hindawi Limited 2014-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2014/302659
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author T. Pereira
A. Gärtner
I. Amorim
A. Almeida
A. R. Caseiro
Paulo A. S. Armada-da-Silva
Sandra Amado
Federica Fregnan
A. S. P. Varejão
J. D. Santos
P. J. Bartolo
S. Geuna
A. L. Luís
A. C. Mauricio
spellingShingle T. Pereira
A. Gärtner
I. Amorim
A. Almeida
A. R. Caseiro
Paulo A. S. Armada-da-Silva
Sandra Amado
Federica Fregnan
A. S. P. Varejão
J. D. Santos
P. J. Bartolo
S. Geuna
A. L. Luís
A. C. Mauricio
Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
BioMed Research International
author_facet T. Pereira
A. Gärtner
I. Amorim
A. Almeida
A. R. Caseiro
Paulo A. S. Armada-da-Silva
Sandra Amado
Federica Fregnan
A. S. P. Varejão
J. D. Santos
P. J. Bartolo
S. Geuna
A. L. Luís
A. C. Mauricio
author_sort T. Pereira
title Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
title_short Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
title_full Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
title_fullStr Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
title_full_unstemmed Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
title_sort promoting nerve regeneration in a neurotmesis rat model using poly(dl-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the wharton’s jelly: in vitro and in vivo analysis
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2014-01-01
description In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.
url http://dx.doi.org/10.1155/2014/302659
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spelling doaj-a680b7334c1e47298d5dc949933218222020-11-24T21:01:40ZengHindawi LimitedBioMed Research International2314-61332314-61412014-01-01201410.1155/2014/302659302659Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo AnalysisT. Pereira0A. Gärtner1I. Amorim2A. Almeida3A. R. Caseiro4Paulo A. S. Armada-da-Silva5Sandra Amado6Federica Fregnan7A. S. P. Varejão8J. D. Santos9P. J. Bartolo10S. Geuna11A. L. Luís12A. C. Mauricio13Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, PortugalCentro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, PortugalDepartamento de Patologia e de Imunologia Molecular, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, PortugalCentro de Estudos de Ciência Animal (CECA), Instituto de Ciências e Tecnologias Agrárias e Agro-Alimentares (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, PortugalDepartamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, PortugalFaculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, PortugalCIPER-FMH, Centro Interdisciplinar de Estudo de Performance Humana, Faculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, PortugalNeuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Regione Gonzole 10, Orbassano, 10043 Turin, ItalyDepartment of Veterinary Sciences, CIDESD, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, PortugalCEMUC, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, PortugalCentro para o Desenvolvimento Rápido e Sustentado de Produto (CDRsp), Instituto Politécnico de Leiria (IPL), Centro Empresarial da Marinha Grande, Rua de Portugal-Zona Industrial, 2430-028 Marinha Grande, PortugalNeuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Regione Gonzole 10, Orbassano, 10043 Turin, ItalyDepartamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, PortugalDepartamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, PortugalIn peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.http://dx.doi.org/10.1155/2014/302659