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BioMed Research International
Volume 2014, Article ID 302659, 17 pages
http://dx.doi.org/10.1155/2014/302659
Research Article

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

1Departamento 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, Portugal
2Centro 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, Portugal
3Departamento 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, Portugal
4Instituto Português de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
5Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Rua Alexandre Herculano No. 321, 4000-055 Porto, Portugal
6Centro 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, Portugal
7Faculdade de Motricidade Humana (FMH), Universidade Técnica de Lisboa (UTL), Estrada da Costa, 1499-002 Cruz Quebrada-Dafundo, Portugal
8CIPER-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, Portugal
9UIS-IPL, Unidade de Investigação em Saúde da Escola Superior de Saúde de Leiria, Instituto Politécnico de Leiria, Morro do Lena, Alto do Vieiro, Apartado 4137, 2411-901 Leiria, Portugal
10Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Regione Gonzole 10, Orbassano, 10043 Turin, Italy
11Department of Clinical and Biological Sciences, University of Turin, 10126 Turin, Italy
12Department of Veterinary Sciences, CIDESD, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
13CEMUC, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
14School of Mechanical, Aerospace and Civil Engineering & Manchester Institute of Biotechnology, The University of Manchester, Manchester M13 9PL, UK

Received 7 February 2014; Revised 27 May 2014; Accepted 29 May 2014; Published 10 July 2014

Academic Editor: Manoor Prakash Hande

Copyright © 2014 T. Pereira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.